SECTION 26 Psychiatric and drug- related disorders

26.1 General introduction 6445 Michael Sharpe
26.1 General introduction 6445 Michael Sharpe
ESSENTIALS
All physicians experience situations in which they need the know-
ledge, skills, and attitudes commonly thought of as belonging to
psychiatry. This section of the book aims to help physicians to ac-
quire these. It includes:  (1) guidance on how to assess medical
patients for psychiatric illness; (2)  information about psychiatric
presentations and the differential diagnoses most relevant to general
medical practice; (3) brief reviews of the psychiatric disorders most
commonly seen in general medical practice and the practical man-
agement of these; (4) guidance on the use of psychotropic drugs and
psychological treatments when given as part of general medical care;
(5) evidence-​based strategies for helping patients who are smoking,
using alcohol excessively, or who are overweight.
Introduction
Physicians face diagnostic and management problems every day for
which even a detailed knowledge of physical disease biology does
not alone provide an answer. In such cases, the knowledge, skills,
and attitudes, usually thought of as ‘psychiatric’ can be helpful.
Examples include the patient with whom doctors find it hard to form
a working relationship, patients who are emotionally distressed, and
patients who present with physical symptoms that are not explained
by identifiable disease.
It is unfortunate that psychiatry and medicine have become so
divorced from one another, and that the subject matter of psych-
iatry has consequently become inaccessible to the physician. The
historical separation of psychiatry from the rest of medicine still
shapes our thinking and practice, and even the organization of our
health services. Indeed, in recent decades, trends in both medicine
and psychiatry have tended to widen this historical split: modern
medicine has focused increasingly on understanding the molecular
biology of disease and less on the whole patient, while psychiatry
has focused increasingly on the psychoses and less on the more
common psychological problems seen in medical patients. More
recently, however, increasing awareness of the fact that medical and
psychiatric illnesses often coexist in the same patient has led to a
strong trend towards the reintegration of psychiatry into general
medical practice.
Psychiatric knowledge that is relevant to general medical prac-
tice includes useful (if imperfect) systems of classifying illnesses
(see next) and evidence for pharmacological and psychological
treatments. Relevant psychiatric skills include the ability to
manage the consultation effectively, to assess the patient’s mental
state as well as their physical state, and to find out about the
patient’s own understanding of their illness. The attitude of non-​
judgemental acceptance of socially deviant behaviour, essential to
the care of severely mentally ill people, may also be helpful to the
physician. It is no secret that some physicians can be dismissive
towards patients whom they perceive as ‘psychiatric’. A  doctor
who is comfortable with and tolerant of patients who have medic-
ally unexplained symptoms, illogical fears, or difficult behaviour
is likely to be both better able to help these patients and to enjoy
their medical practice.
Although most physicians do a great deal of what may be referred
to as ‘psychiatry’ themselves, specialist psychiatric help is not infre-
quently required. Unfortunately, appropriate and useful psychiatric and
psychological services are frequently hard to access. This reflects ad-
ministrative and geographical separation of services and often a lack of
understanding of the pressures of acute medical care by those working
in mental health services. Fortunately, in recent years there has been a
slow but steady growth in general hospital-​based psychiatry and psych-
ology services that are specifically dedicated to helping physicians meet
the needs of their patients. These services offer improved access and
greater acceptability to patients than general psychiatry services, and
also are better equipped to manage the problems that are common in
medical patients. These services are called liaison psychiatry (linking
psychiatry and medicine), psychological medicine (specializing in psy-
chological aspects of medicine), and in parts of Europe, psychosomatic
medicine (medicine that links mind and body).
The chapters
The sections that follow aim to provide a practical, and hope-
fully accessible, summary of those aspects of the assessment and
26.1
General introduction
Michael Sharpe
section 26  Psychiatric and drug-related disorders
6446
management of patients conventionally termed ‘psychiatric’, but
which are in fact central to the practice of all of medicine. They
include:
•	 Guidance on how to do an efficient psychiatric assessment of a
medical patient.
•	 Information about those psychiatric presentations most relevant
to general medical practice, including confusion, low mood, med-
ically unexplained symptoms, and self-​harm, and the differential
diagnosis for each.
•	 Brief reviews of the psychiatric diagnoses most commonly encoun-
tered in general medical practice including organic mental dis-
orders (delirium and dementia), emotional disorders (depression
and anxiety), severe reactions to stressors, somatic symptom dis-
order, personality disorders, and eating disorders, as well as more
basic coverage of the less commonly encountered but important
psychiatric diagnoses of bipolar disorder and schizophrenia.
•	 Guidance on the use of psychotropic drugs and psychological
treatments when given as part of general medical care.
•	 Useful advice on how to help patients with the common and
clinically important problems of alcohol and substance misuse,
obesity, and smoking.
While some readers might regard this section of the book as
merely an unnecessary ‘add on’ to the core contents of a medical
textbook, of questionable relevance to the practising physician,
I hope most will find it helpful in understanding and meeting their
patients’ needs.
A note on the classification of psychiatric
diagnoses
The most widely used classification of psychiatric diagnoses in the
United Kingdom and United States is the American Psychiatric
Association Diagnostic and Statistical Manual, known as DSM.
Currently in its fifth edition, it is known as DSM-​5.
The other classification frequently used for coding diagnoses
is the section in the World health Organization’s International
Classification of Diseases known as ICD. Currently in its tenth edi-
tion, it is referred to as ICD-​10.
FURTHER READING
American Psychiatric Association (2013). Diagnostic and statis-
tical manual of mental disorders, 5th edition (DSM-​5). American
Psychiatric Press, Washington D.C.
Geddes J, Andreason N, Goodwin G (eds) (2017). The new Oxford text-
book of psychiatry. Oxford University Press, Oxford.
Levenson JL (ed) (2018). Textbook of psychosomatic medicine and
consultation-liaison psychiatry, 3rd edition. American Psychiatric
Association, Washington D.C.
Lloyd G, Guthrie E (eds) (2011). Handbook of liaison psychiatry.
Cambridge University Press, Cambridge UK.
Sharpe M (2010). Psychiatry in general medical settings. In: Johnstone
EC, et  al. (eds), Companion to psychiatric studies, 8th edition.
Churchill Livingstone. Edinburgh.

26.2 The psychiatric assessment of the medical pat
26.2 The psychiatric assessment of the medical patient 6447 Jane Walker, Roger Smyth, and Michael Sharpe
ESSENTIALS
Medically ill patients often have psychiatric illness. Physicians can
and should detect and diagnose these illnesses during their standard
medical assessment. All that is required is knowledge of key ques-
tions to ask patients, awareness of the clinical signs that may be ob-
served, and an appreciation of the value of additional information
from patient’s relatives, other clinicians, and the medical record.
The aims are to detect and diagnose psychiatric disorders; as-
sess the risk of self-​harm or harm to others; establish the need for
treatment or referral for a psychiatric opinion; provide the basis for
clear and effective communication with a psychiatrist; and to com-
municate to the patient that you are interested in all aspects of their
suffering and thereby establish a clinically effective relationship
with them.
The sources of information are relevant history from the patient
supplemented with specific questions; the clinician’s observation of
the patient during the consultation; and relevant clinical records and
reports from others (e.g. relatives, nursing staff).
The minimum psychiatric assessment comprises the relevant his-
tory and key questions based on the patient’s presenting complaint,
history, and observation; observation of the patient during the con-
sultation for signs of mental illness; composition of a list of any psy-
chotropic medication the patient is taking; an assessment (where
appropriate) of risk of self-​harm and harm to others; obtaining rele-
vant information from relatives and other clinicians as needed; and
the use (if required) of scales and tests, such as those for assessing
cognitive impairment.
Introduction
A basic psychiatric assessment is essential for all medical patients.
This is because mental illness is so common in patients presenting
to physicians. In fact, rather than physical and mental illnesses af-
fecting different populations of patients, as is often assumed, they
tend to occur together in the same individuals. For example, as many
as half of the patients admitted to a medical ward will have a mental
illness, most commonly delirium, dementia, depression, anxiety,
substance misuse, and somatic symptom disorder.
All physicians therefore need to know how to recognize the symp-
toms and signs of common mental illnesses. This process is often,
but wrongly, thought to be distinct from the standard medical as-
sessment, as well as being time-​consuming and even risky. In fact,
assessing patients for mental illness can be, and should be, an inte-
gral part of the medical assessment. It need not be time-​consuming
and doing it will reduce rather than increase any risk the patient
poses to themselves or others.
The standard psychiatric assessment is traditionally divided into
history taking and the ‘mental state examination’, which parallel
medical history taking and physical examination. In practice, how-
ever, the mental state examination is not a separate procedure done
after taking the history, but is largely accomplished by observing
the patient while taking the history. For example, a patient with
depression may say that they feel low (history) and be observed
(examination) to look tearful and to speak slowly while giving
their history.
The psychiatric assessment
The psychiatric assessment has several aims and uses multiple
sources of information.
Aims
These are to:
•	 Detect and diagnose psychiatric disorders
•	 Assess the risk of self-​harm or harm to others
•	 Establish the need for treatment or referral for a psychiatric
opinion
•	 Provide the basis for clear and effective communication with a
psychiatrist
•	 Communicate to the patient that you are interested in all aspects
of their suffering and thereby establish a clinically effective rela-
tionship with them
Sources of information
These are:
•	 Relevant history from the patient supplemented with specific
questions
26.2
The psychiatric assessment of
the medical patient
Jane Walker, Roger Smyth, and Michael Sharpe
section 26  Psychiatric and drug-related disorders
6448
•	 The clinician’s observation of the patient during the consultation
•	 Relevant clinical records and reports from others (e.g. relatives,
nursing staff)
What to ask and look for
The minimum psychiatric assessment comprises: (a) the relevant
history and key questions based on the patient’s presenting com-
plaint, history and observation; (b) observation of the patient during
the consultation for signs of mental illness; (c) a list of any psycho-
tropic medication the patient is taking; (d) where appropriate, an
assessment of risk of self-​harm and harm to others; (e) relevant in-
formation from relatives and other clinicians as needed; (f) use of
scales and tests, such as those for assessing cognitive impairment,
if required.
The following sections summarize the core symptoms, signs,
and additional information useful in detecting and diagnosing
the psychiatric disorders most commonly seen in general medical
practice.
Depression
Core symptoms of depression
The two core symptoms of depression are pervasive low mood and
loss of interest or pleasure (also called anhedonia).
To detect low mood, ask the patient how they have been feeling.
Be aware that when asked this, medically ill patients often assume
they are being asked about their physical symptoms (e.g. pain) so a
qualifier (e.g. ‘how have you been feeling in yourself, how has your
mood been?’) may be required. It is also important to be aware that
people use different words for low mood such as sad, unhappy, or
down. If low mood is suspected, ask the patient just how low their
mood has been, using their own word for low mood, and then en-
quire how much of the day and for how many days or weeks they
have felt like that to find out how pervasive it has been.
To detect anhedonia, find out if the patient has experienced
a change in interest in or enjoyment of activities, ask about the
things they usually enjoy doing and whether they are still able to get
pleasure from these. For the person who is hospitalized or disabled,
it is useful to focus on enjoyment of simple activities such as reading
or visits from family or friends, and to ask whether they would like to
be doing their usual activities if they were able. Box 26.2.1 suggests
how to ask these questions.
Signs of depression
A patient with depression may appear to have lost interest in their
appearance or self-​care. They may move slowly, look downcast, and
fail to make eye contact, have a sad facial expression or even cry.
They may talk slowly with little intonation and with a negative, pes-
simistic, or even hopeless content to their speech.
Other sources of information
An account of change in behaviour, including reduced activity and
interest, from an informant is useful, as the patient may not always
recognize the change in themselves.
The medical records may indicate a history of depression, which
is typically a relapsing disorder. There are many self-​rated ques-
tionnaires to determine the severity of depressive symptoms; a
commonly used one, which can also be used as an initial screen for
depression, is the PHQ-​9 (Box 26.2.2).
Mania
Core symptoms of mania
Manic episodes occur as part of bipolar disorder. The core symptoms
of mania are abnormally elevated or irritable mood and greatly in-
creased energy. These symptoms are severe enough to cause marked
impairment in the patient’s ability to function at work or socially. To
detect mania, recognize if the patient spontaneously reports their
mood as unusually good or irritable, their energy as particularly
high or their need for sleep greatly decreased. They may describe
grandiose ideas (e.g. being able to control the weather) and unchar-
acteristic behaviour such as spending beyond their means.
Signs of mania
A patient with mania may be distractible or restless, and be fidgeting
or pacing about the room. They may appear ‘infectiously cheerful’ or
easily irritated. Their behaviour may be overfamiliar and disinhib-
ited, for example, sitting in the physician’s chair, playing with equip-
ment, or making sexual suggestions to staff. They are likely to be
talkative with rapid speech that is difficult to interrupt and may be
fragmented in content.
Other sources of information
The patient’s account may be unreliable and an account from a close
relative or friend is an essential source of information on both pre-
vious history and recent behaviour. The medical records may indi-
cate a history of bipolar disorder, which is a relapsing condition.
Anxiety
Patients are often anxious during medical consultations. Anxiety
only becomes pathological when it is persistent and severe, or leads
to avoidance of important activities or situations.
Questions to ask about anxiety are suggested in Box 26.2.3.
Core symptoms of anxiety
The core symptoms of anxiety are feeling fearful, tense, or on edge.
These symptoms may be due to a generalized anxiety disorder (when
Box 26.2.1  Asking about depression
‘How would you describe your mood recently?’
Some patients find it difficult to describe their current mood. Ask them
if they have felt down or low at all. Then ask how low—​a scale of 1 to 10
can be helpful. Ask them for how long, and for how much of the time,
has their mood been as low as this.
‘Can you still enjoy things you used to enjoy?’
Depressed patients typically describe lack of interest in previously en-
joyed activities. If their medical condition is disabling, ask about non-​
physically demanding activities that they can still do (e.g. watching TV or
reading) and whether they would like to be doing their usual activities if
they were physically able.
26.2  The psychiatric assessment of the medical patient
6449
they are present most of the time), panic disorder (when they occur
along with physical symptoms during discrete severe episodes),
phobic disorder (when the anxiety occurs in specific situations that
are often avoided) or obsessive-​compulsive disorder (when associ-
ated with recurrent intrusive thoughts and compulsive actions).
To detect an anxiety disorder, ask the patient how often they feel
worried, anxious, or afraid. Find out whether the anxiety occurs in
specific situations and whether it is preventing them from doing
things, such as leaving the house, being able to relax, or attend hos-
pital appointments. Ask if there is anything specific that they are
concerned about and what they do when they become anxious.
When asking about panic attacks enquire about severe anxiety
that has a sudden onset with physical symptoms, often accompanied
by a fear of collapse or even sudden death.
Asking what the patient thinks about when they feel anxious may
reveal obsessions, which are recurrent unwanted thoughts that pa-
tients are often embarrassed to describe. In obsessive-​compulsive
disorder these occur along with compulsions; repetitive and illogical
actions that relieve the anxiety and which can be elicited by asking
what the patient does when they feel anxious. For example, a person
with obsessional thoughts about spreading infections may compul-
sively wash or disinfect their hands for hours on end.
Signs of anxiety
During the consultation, patients with anxiety may look tense,
sweaty, or shaky. They may repeat questions and seem preoccu-
pied with the worst outcomes. If they have a panic attack during the
consultation, they will show a sudden onset of anxiety, often with
shaking and hyperventilation, that subsides rapidly. Anxiety related
to a phobia, for example, of needles, may manifest during the con-
sultation at the mention of these. Some patients have an anxious pre-
occupation with having a serious illness (health anxiety) and may
repeatedly request reassurance or investigations for this. Finally, evi-
dence of compulsions such as handwashing may be seen on physical
examination as red dry hands.
Other sources of information
An account from a close relative is useful, particularly in quantifying
the degree of avoidance. The medical records may reveal a history of
anxiety. Frequent attendance at the hospital or clinic may indicate
anxiety about having a serious illness such as cancer. A self-​rated
questionnaire, such as the GAD-​7, can be used to determine the se-
verity of generalized anxiety symptoms (Box 26.2.4).
Substance misuse
Excessive and often harmful use of alcohol is common in medical
patients. Some patients misuse other drugs both prescribed (such
as opiates) and illicit (such as so-​called legal highs). It is therefore
useful to routinely ask patients about their alcohol and drug intake,
Box 26.2.2  The 9-​item Patient Health Questionnaire (PHQ-​9)
Over the last week how often have you been bothered by the following problems?
Not at all
(0)
Several days
(1)
More than half the days
(2)
Nearly every day
(3)
Little interest or pleasure in doing things
□
□
□
□
Feeling down, depressed, or hopeless
□
□
□
□
Trouble falling or staying asleep, or sleeping too much
□
□
□
□
Feeling tired or having little energy
□
□
□
□
Poor appetite or overeating
□
□
□
□
Feeling bad about yourself, or that you are a failure, or
have let yourself or your family down
□
□
□
□
Trouble concentrating on things, such as reading the
newspaper or watching television
□
□
□
□
Moving or speaking so slowly that other people have
noticed. Or the opposite—​being so fidgety and restless
that you have been moving around a lot more than usual
□
□
□
□
Thoughts that you would be better off dead, or of hurting
yourself in some way
□
□
□
□
Scores of 10, 15, and 20 are the cut-​off points for moderate, moderately severe, and severe depression, respectively
Box 26.2.3  Asking about anxiety
‘Recently, have you been feeling more anxious than usual?’
If yes, ask the patient to describe how severe the anxiety is and how
often it is present. Also ask when the symptoms began and what was
happening at that time.
‘Do any particular places or situations make you anxious?’
Establish first whether the anxiety is continual or episodic. If the latter,
enquire about those environments or situations that cause the exacerba-
tions. This may indicate specific phobias.
‘Have you ever had a panic attack?’
Ask the patient to describe to you what their attacks of anxiety are like.
A panic attack is sudden in onset with gradual resolution over the subse-
quent 30 minutes. The patient experiences a sensation of extreme anx-
iety and fear, usually accompanied by physical manifestations of anxiety
such as hyperventilation (which may induce paraesthesia), dizziness,
sweating, and palpitations.
section 26  Psychiatric and drug-related disorders
6450
especially when the reason they have presented, such as an accident
or liver disease, is known to be associated.
Core symptoms of substance misuse
To detect substance misuse, ask the patient whether they drink alcohol
and whether they take any drugs, other than the ones prescribed for
them. To get an estimate of alcohol intake, ask the patient to go through
what they have drunk each day for the last week, noting binges as well
as a steady daily intake. The core symptoms of alcohol use disorder are
drinking excessively despite negative consequences, unsuccessful at-
tempts to cut down intake, cravings, tolerance, and drinking to prevent
withdrawal symptoms. Patients with a history of daily or near-​daily
drinking, with morning drinking, and those regularly drinking more
than 15 units of alcohol daily should be considered at high risk of with-
drawal symptoms and delirium tremens.
Signs of substance misuse
There may be obvious signs such as smelling of alcohol, appearing in-
toxicated or even carrying alcohol (the clink of bottles in the carrier
bag) or other drugs into the hospital. Patients may also show signs
of alcohol withdrawal such as shaking, sweating, hallucinations, and
seizures. Physical examination may reveal other relevant signs such
as evidence of frequent falls, liver disease, or needle marks.
Other sources of information
People notoriously underestimate their alcohol consumption and an
account from an informant is valuable corroboration. Medical re-
cords may indicate diagnoses suggestive of alcohol or drug induced
harm such as liver disease. The four-​item CAGE questionnaire can
be used as a screen for problem drinking. In the acute and emer-
gency setting, an important issue is the identification of patients
at risk of the development of alcohol withdrawal; this is especially
likely in those who the final answer yes to the last question of the
CAGE—​drinking in the morning to prevent withdrawal symptoms.
The CAGE questions are listed in Box 26.2.5.
Psychosis
These include both the so-​called ‘functional’ psychoses (schizo-
phrenia, acute psychotic episodes, delusional disorder and severe
depression or mania) and in the ‘organic’ psychoses (in delirium,
dementia, and states resulting from brain injury and substance
misuse). In medical contexts, new onset psychotic phenomena are
more likely to be a symptom of organic disturbance of brain func-
tion, particularly delirium, dementia, or drug and alcohol intoxica-
tion or withdrawal, than a functional psychosis.
Core symptoms of psychosis
The core symptoms of psychosis are delusions and hallucinations.
Delusions are fixed false beliefs that often have a bizarre quality,
such as thinking the nurses are secret agents. Hallucinations are
false experiences (although they seem real and to have come from
the outside world to the patient), in any sensory modality, such
as seeing rats that are not there or hearing voices when no one
is present. It is neither necessary nor appropriate to do routine
screening for psychotic phenomena. Asking medical patients
about ‘voices’ or ‘odd ideas’ is unlikely to yield much useful in-
formation and may perplex them. However, if the history, obser-
vation, or other sources of information suggests such symptoms,
they should be carefully enquired after. Questions to ask are listed
in Box 26.2.6.
Signs of psychosis
A patient who has a psychosis may appear to be responding to hal-
lucinations, for example, looking at places in the room where there
are no people or movements or talking to people who are not there.
They may behave bizarrely or appear frightened because of their de-
lusional beliefs. Signs suggesting an organic psychosis are impaired
alertness, visual hallucinations, and a fluctuating mental state.
Box 26.2.4  The 7-​item Generalized Anxiety Questionnaire (GAD-​7)
Over the last week how often have you been bothered by the following problems?
Not at all
(0)
Several days
(1)
More than half the days
(2)
Nearly every day
(3)
Feeling nervous, anxious, or on edge
□
□
□
□
Not being able to stop or control worrying
□
□
□
□
Worrying too much about different things
□
□
□
□
Trouble relaxing
□
□
□
□
Being so restless it is hard to sit still
□
□
□
□
Becoming easily annoyed or irritable
□
□
□
□
Feeling afraid as if something awful might happen
□
□
□
□
Scores of 5, 10, and 15 are the cut-​off points for mild, moderate, and severe anxiety respectively
Box 26.2.5  The CAGE questionnaire
C: Have you ever felt you should Cut back on your drinking?
A: Has anyone ever Annoyed you by criticizing your drinking?
G: Have you ever felt Guilty about your drinking?
E: Have you ever had a drink early in the morning as an Eye-​opener?
More than two positive responses suggests possible at-​risk drinking and
should prompt further assessment.
N.B. The ‘Cage +2’ adds two additional questions:
What is the most alcohol you have drunk in a single day?
What is the most alcohol you have drunk in a single week?
26.2  The psychiatric assessment of the medical patient
6451
Other sources of information
History from an informant is crucial. While psychotic illnesses are
very variable in presentation, within an individual patient each epi-
sode tends to be similar. Therefore asking what symptoms occurred
during the most recent relapse and whether similar symptoms are
present now is a useful method of enquiry. Medical records may in-
dicate a previous history of psychotic illness or the prescription of
antipsychotic drugs.
Cognitive impairment
Impairment in cognitive function is very common in medical pa-
tients. The chronic form called dementia becomes more preva-
lent with increasing age. The acute form called delirium (or acute
confusional state) is a common complication of many medical dis-
orders and is especially common in those with some pre-​existing
cognitive impairment.
Core symptoms of cognitive impairment
The core symptom of cognitive impairment is the inability to process
information. This may manifest as failing memory or the inability
to complete simple tasks such as making a cup of tea. Patients with
cognitive impairment may also be unable to behave in a socially ap-
propriate way. Given the high frequency of, and risk resulting from,
undetected cognitive impairment it should be actively considered in
all elderly patients. At a minimum, patients should be asked simple
questions to determine their orientation to time, place, and person.
Signs of cognitive impairment
The patient who is cognitively impaired may appear confused and
may fail to understand the nature of the consultation or to recall
previously provided information. The delirious patient may appear
drowsy and have an obviously reduced conscious level. It is im-
portant to be aware that a polished social façade may mask signifi-
cant cognitive deficits.
Other sources of information
History from family and friends, carers, or other professionals is cru-
cial to both determining the severity of the impairment and whether
it is of new onset. It also allows the clinicians to establish how well the
patient functions at home when they are unable to give an accurate
history themselves. Medical records are often useful in determining
the duration of any impairment. The Abbreviated Mental Test
(AMT) is a short 10-​item bedside screening test for cognitive im-
pairment (Box 26.2.7). For practical purposes, however, how much
any cognitive impairment affects the patient’s real-​world function
is often more important than absolute scores in standardized tests.
For patients found to have cognitive impairment, a more detailed
assessment may be required. This should include an assessment of
their current functional level, a review of their previous cognitive
state and function and the likely cause for any decline. Many bedside
tests of cognitive function are available such as the 30-item Montreal
Cognitive assessment (MoCA).
Eating disorders
The most common eating disorders are anorexia nervosa and
bulimia nervosa. In both of these conditions, the patient strives for
weight control; in the former, they are notably thin and in the latter,
they are not.
Core symptoms of eating disorders
The core symptom of anorexia nervosa is an intense fear of becoming
fat, which leads to severe dietary restriction and low body weight. The
core symptoms of bulimia nervosa are recurrent episodes of binge eating
with compensatory behaviours intended to prevent weight gain. These
symptoms may be detected by asking the patient in detail about their
dietary intake, use of laxatives or diuretics and daily exercise regimen, as
well as their thoughts about their body size and shape.
Signs of eating disorders
Low body weight is the most obvious sign of anorexia nervosa.
Other signs of eating disorders include eroded dental enamel and
calluses on the knuckles (Russell’s sign) from self-​induced vomiting,
lanugo hair, and dry skin.
Other sources of information
A history from the patient’s general practitioner and family is essen-
tial. Nursing staff may note that the patient repeatedly refuses food
while in hospital, makes trips to the bathroom immediately after
eating, or is seen vomiting or hiding vomit. Medical records may
indicate complications of eating disorders, such as recurrent elec-
trolyte disturbances.
Box 26.2.6  Asking about psychotic symptoms
‘Have you heard voices when there was no one about?’
Hallucinations can occur in any modality of sensation, however auditory
hallucinations are characteristic of schizophrenia and similar illnesses.
They are experienced as coming from external space rather than ‘inside
my head’. Their quality, content, and degree of associated distress should
be explored.
‘Do you ever feel that people are talking about you, or spying on you, or
trying to harm you?’
Delusions are another core feature of psychotic illnesses and can have a
wide variety of contents. Referential and persecutory delusions are com-
monly seen. The content of the belief and the patient’s rationale for be-
lieving it should be explored. A characteristic of true delusions is that they
are rigidly held and not amenable to rational argument.
Box 26.2.7  The Abbreviated Mental Test (AMT)
What is your age? (1 point)
What is the time to the nearest hour? (1 point)
Give the patient an address, and ask him or her to repeat it at the end of
the test. (1 point)
(e.g. 42 West Street)
What is the year? (1 point)
What is the name of this place? (1 point)
Can the patient recognize two persons (e.g. doctor, nurse)? (1 point)
What is your date of birth? (day and month sufficient) (1 point)
In what year was the 9–​11 terrorist attack? Or year of the First World
War? (1 point)
Name the present prime minister or president of the United States.
(1 point)
Count backwards from 10 down to 1. (1 point)
A score of 7 or less suggests some cognitive impairment
section 26  Psychiatric and drug-related disorders
6452
Stress-​related disorders
Stress-​related disorders, by definition, occur in response to a trau-
matic or stressful event. These include acute stress disorder and
adjustment disorder in which the stressor is current, and post-​
traumatic stress disorder. The latter may be less obvious and should
be suspected when the patient has been or is subject to a major
stressor such as a severe car accident.
Core symptoms of stress-​related disorders
The core symptoms of post-​traumatic stress disorder (PTSD) are
recurrent, intrusive memories of the event, including ‘flashbacks’,
distressing event-​related dreams, problems with concentration and
hypervigilance, and significant avoidance of things that remind the
patient of the event. To detect these symptoms, ask how the patient is
coping since the event, whether they are sleeping well and how they
are generally feeling about it.
Signs of stress-​related disorders
Patients with PTSD may go to great lengths to avoid distressing
memories, for example, driving miles out of their way to avoid the
site of a car crash. They may find it difficult to concentrate on the
consultation or be noted to have repeated nightmares.
Other sources of information
The medical records may indicate the nature of the stressor. The
timing from the date of the event is important in determining the
type of stress-​related disorder and therefore appropriate treatment.
Personality disorders
The core features of personality disorders are extreme and maladap-
tive personality traits that cause difficulty or distress to the person
themselves or to others. Physicians may be alerted to the possible
diagnosis of a personality disorder in patients who recurrently self-​
harm, show extreme responses to events, or have unusual ways of re-
lating to clinical staff. The diagnosis of personality disorder requires
that the patient have a long history of similar behaviours and the
exclusion of other psychiatric diagnoses. It therefore requires a thor-
ough psychiatric assessment.
Somatic symptom disorder
The core feature of somatic symptom disorder is concern about
physical symptoms that appears to be out of proportion to the se-
verity of any associated disease. The concern may manifest as dis-
proportionate preoccupation, distress, and disability. The symptoms
may be medically unexplained, but somatic symptom disorder also
co-​occurs with medical disease. Physicians may be alerted to the
possible diagnosis of severe somatic symptom disorder during the
physical examination by multiple operation scars and from the med-
ical records by a history of frequent attendance at medical services
and numerous negative (and often repeated) investigations. Severe
somatic symptom disorder can be difficult to manage and requires
collaboration between all the physicians involved in the patient’s
care; referral to liaison psychiatry can be helpful in confirming the
diagnosis and helping to construct a management plan.
Risk of self-​harm and suicide
When to ask
While it would not be appropriate to ask everyone about suicidal in-
tent or thoughts of self-​harm, this should always be done when there
is evidence of depression, and especially when the patient has ex-
pressed thoughts that they would be better off dead, feelings of hope-
lessness, or when there is a history of self-​harm. It is important to be
aware that sensitive enquiry will not ‘put the idea into the patient’s
head’ or increase the risk of self-​harm or suicide. Rather it will pro-
vide an opportunity to address and consequently reduce the risk.
How to ask
It may seem intrusive to ask a patient directly about suicidal thoughts,
hence it is often best to ask a graded series of questions, starting with
‘How do you feel about the future?’ Then ‘Has it ever got so bad you
thought life is not worth living?’, then ‘Have you ever thought about
ending your life?’ and then, if appropriate, ‘What plans have you
made?’ Examples of questions are shown in Box 26.2.8.
Signs of previous self-​harm
Physical examination may reveal marks or scars from previous self-​
inflicted injuries.
Other sources of information
Medical records may reveal a history of self-​harm. An account from
a close relative is valuable is learning about recent attempts of pre-
parations. This may include hoarding pills or searching the internet
about how to commit suicide.
Box 26.2.8  Asking about suicidal ideas
‘How do you feel about the future?’ ‘Do you ever feel hopeless about it?’
Most patients will retain a degree of optimism about eventual improve-
ment or recovery, even with significant medical illness. A sense of hope-
lessness towards the future can be associated with depressed mood and
suicidal thoughts, and should prompt further exploration.
‘Have you ever felt that it hasn’t worth going on, or that life was not worth
living?’
These thoughts can develop from a sense of hopelessness and are often
associated with thoughts of death which may be passive (e.g. ‘it would
be nice to go to sleep and not wake up’), or active—​where the patient
considers taking steps themselves to end their life.
‘Have you ever thought about ending your life?’
If the patient answers yes, enquire about the frequency of these
thoughts—​are they fleeting and rapidly dismissed, or more prolonged?
Are they becoming more common?
‘Have you thought about how you would do it?’
Explore which methods the patient has considered and what prepar-
ations they have made. Violent suicide methods (e.g. hanging, jumping,
firearms) are particularly concerning. Repeated visualization of the act of
suicide is associated with increased risk.
‘Have you ever tried to take your own life?’
A history of previous suicidal actions increases the current risk. A recent
concealed attempt (e.g. overdose) may necessitate additional medical
assessment.
26.2  The psychiatric assessment of the medical patient
6453
Risk to others
When to ask
It is important to consider risk to others when the patient has delusional
beliefs that other people are trying to harm them in some way, are not
who they say they are, or are trying in some way to thwart them. Patients
with depression are at much greater risk to themselves than to others.
However, women with postnatal depression and patients with particu-
larly dependent relationships may have thoughts of ending the lives of
their loved ones as well as their own. Patients with personality disorders,
in particular antisocial personality disorder, may sometimes pose a risk
to others and if threats are made, these should be explored.
How to ask
As with suicidal thoughts, a graded approach is usually best. Prefacing
questions with an acknowledgement of the patient’s situation, such as,
‘this must be very difficult for you’ can be followed by, ‘sometimes in
this kind of situation people start to think about how they could harm
the people that are persecuting them’ or ‘sometimes when people feel
this bad and they are thinking about ending their lives, they also think
about ending their families’ lives’, have you had any thoughts like that?’
When to seek help
If you have any concerns that the patient might pose a risk to them-
selves or to others, even if the patient ‘says the right things’, it is essen-
tial to seek a psychiatric opinion.
Psychotropic drugs
Many patients are taking psychotropic drugs. As well as asking
the patient about these, it is important to clarify from records or
their usual clinician, what they are prescribed for their psychi-
atric condition. Remember to ask about depot medications; these
are long acting antipsychotic drugs, often given by fortnightly
injection. Also enquire about dosages and pick-​up routines for
substitute drugs prescribed in addictions—​from which pharma-
cist are they dispensed, has the prescription been stopped while
the patient is in hospital, and does the patient take all of their
prescription.
FURTHER READING
American Psychiatric Association (2013). Diagnostic and statis-
tical manual of mental disorders, 5th edition (DSM-​5). American
Psychiatric Press, Washington, D.C.
Kroenke K, et al. (2010). The patient health questionnaire somatic,
anxiety, and depressive symptom scales: a systematic review. Gen
Hosp Psychiatry, 32, 345–​59.
Nasreddine ZS, et  al. (2005). The Montreal Cognitive Assessment,
MoCA: a brief screening tool for mild cognitive impairment. J Am
Geriatr Soc, 53, 695–​9.
Trzepacz PT, Baker RW (1993). The psychiatric mental status examina-
tion. Oxford University Press, New York, NY.

26.3 Common psychiatric presentations in medical p
26.3 Common psychiatric presentations in medical patients 6454 26.3.1 Confusion 6454 Bart Sheehan and Thomas Jackson
CONTENTS
26.3.1	 Confusion  6454
Bart Sheehan and Thomas Jackson
26.3.2	 Self-​harm  6457
Kate E.A. Saunders and Keith Hawton
26.3.3	 Medically unexplained symptoms  6460
Michael Sharpe
26.3.4	 Low mood  6462
Jane Walker
26.3.1  Confusion
Bart Sheehan and Thomas Jackson
ESSENTIALS
Confusion is a very common presentation in medical patients, espe-
cially in older people. It may, but does not always, indicate dementia.
Delirium describes a typically brief, fluctuating, and transient state of
confusion, which requires a vigorous and urgent hunt for the cause
or causes. This is often, but not always, an infection or vascular event.
The potential role of prescribed drugs in causing confusion should
not be forgotten, and other causes of apparent confusion include de-
pression. Making the diagnosis might take time, and in the meantime
it is important to ensure that the physical and nursing arrangements
for care keep the patient safe from harm.
Introduction
The term confusion is defined as ‘The state of being bewildered or
unclear in one’s mind about something’, from the Latin confudere
‘mingle together’. In clinical settings the term is widely used but
not defined, being employed to refer to chronic cognitive impair-
ment (usually dementia) or acute cognitive impairment (usually de-
lirium). The term is used so frequently as to justify a standardized
clinical approach in assessing patients.
Common presentations
Vignette 1—​A presentation of delirium
A 91-​year-​old female care home resident presents to the emergency
department. Her GP has seen her earlier in the day and sends a note
stating she is ‘off legs, confused.?UTI’. She was prescribed trimetho-
prim 2 days before. She fluctuates in alertness, and cannot sustain at-
tention to questions. A brief examination of lungs, abdomen, limbs,
and heart sounds is unremarkable. Further history indicates that the
confusion is new. A diagnosis of delirium is made secondary to a
urinary tract infection unresponsive to trimethoprim.
Vignette 2—​A presentation of dementia
A 79-​year-​old man is admitted from his own home with ‘confusion
and agitation’. He has had good physical health, although the referral
states he has had ‘memory loss’. He looks after his disabled wife. She
reports that over the last 18 months he has begun to care less well for
himself, having previously always been very smart. He mixes up days
and dates and she has had to take over management of household
bills. MRI brain scans show generalized atrophy with more prom-
inent volume loss in hippocampal area. A diagnosis of dementia due
to Alzheimer’s disease is made.
Relevant psychiatric disorders
While dementia will often be the diagnosis, especially in older
people, delirium is an important differential diagnosis as it re-
quires vigorous further assessment to identify easily treatable
causes such as infection and alcohol withdrawal. Depression
may also sometimes present with apparent confusion—​so-​called
depressive pseudo-​dementia—​and is important to identify as
it is also treatable. The main differential diagnosis is shown in
Box 26.3.1.1.
26.3
Common psychiatric presentations
in medical patients
Box 26.3.1.1  Main differential diagnosis of confusion
•	 Dementia
•	 Delirium (many causes including prescribed drugs, hypoglycaemia &
hypoxia)
•	 Alcohol or drug intoxication or withdrawal
•	 Depression (depressive pseudo-​dementia)
26.3.1  Confusion
6455
Assessment
History
The history is the paramount investigation with confused patients
(Box 26.3.1.2).
For obvious reasons a collateral history is always needed—​from
family, primary care physician, care home staff, or simply from pre-
vious medical notes. The observations of the patient’s behaviour
by experienced ward staff may also be invaluable—​especially in
detecting fluctuation and inattentiveness.
The first question is when the patient changed from their baseline
mental state. A long history suggests an established dementia. The
family or care staff may be aware of the diagnosis and/​or the patient
may have been prescribed antidementia medication. Patients with
undiagnosed dementia often have a history of progressive short-​
term memory loss, disorientation in time, dysphasia, impairment of
activities of daily living including instrumental activities (e.g. using
phone/​cooking/​doing bills) and more basic activities (e.g. dressing/​
toileting). There may also be a history of personality change such as
a coarsening of manners or the development of apathy.
Where the diagnosis is that of a new delirium there will either be
little or no evidence of impairment in background cognition or daily
activities, or a rapid deterioration from a well-​established baseline
level of impairment when the delirium is superimposed on a de-
mentia. Collateral history will reveal a rapid onset of mental change
characterized by vague, inattentive responses, periods of change-
able alertness, forgetfulness, disorientation, muddled speech, and
changes in mood. There may have been frank psychotic experiences
including abnormal visual experiences or paranoid delusions. Key
questions to ask are if there were signs of physical illness, a change
in medication, or a change in physical location in the days leading to
the new mental state.
Examination
Appearance and behaviour
The patient may be dishevelled or show self-​neglect. There may be
obvious clues to sources of confusion (e.g. a non​functional hearing
aid, wheeziness/​productive cough, or a Parkinsonian tremor sug-
gesting Lewy body dementia). In delirium, patients may be aroused
and alert, or sleepy. They may show sustained attention during assess-
ment (in dementia) or be unable to sustain attention (in delirium).
Speech
Patients with dementia are likely to show expressive dysphasia
(difficulty with production of speech) or may fail to understand
commands (receptive dysphasia). Patients with certain causes of
confusion (e.g. Parkinson’s disease) may show slurring of speech.
Patients with depression may show retardation of speech with low
volume answers which are considerably delayed.
Mood
Patients with acute confusion due to delirium are typically bewil-
dered and may appear frightened. Patients with depression look sad
or irritable, with a lack of expected emotional reactivity. Patients
with dementia are usually normal in effect, though may become la-
bile, agitated, or disinhibited as the condition advances.
Thoughts
Depressive ideas (e.g. depressive delusions of hopeless, guilty, or ni-
hilistic type) suggest a severe depressive disorder. Patients with de-
lirium may report fractured paranoid ideas (e.g. of people planning
to hurt them), but these are rarely sustained. Patients with dementia
usually report normal thought content, though may confabulate (re-
port plausible but untrue accounts of their recent experiences).
Perceptions
In dementia, hallucinations are rare except for dementia with Lewy
bodies where visual hallucinations are common. Abnormal visual
experiences are however common in delirium. Patients currently
experiencing visual hallucinations will be seen attending to phe-
nomena unseen by the observer. Mood congruent auditory hallu-
cinations (e.g. voices commanding the patient to self-​harm) are a
rare but highly suggestive feature of severe depressive episodes.
Cognition
By definition, cognition is impaired in confused patients. Commonly
used short assessments of cognition include the Abbreviated Mental
Test Score (AMTS), which assesses cognition in about three min-
utes and is reasonably sensitive to change. On retesting, patients
with delirium will usually show some fluctuation with improvement
and deterioration, while patients with simple dementia will usually
be stable between assessments. Patients with depression may score
poorly, but will show a lack of effort, for example refusing to attempt
tests of recall or of sustained attention like counting down.
More detailed tests of cognition are useful in describing cross sec-
tional cognitive impairment, for example the Montreal Cognitive
Assessment (MoCA), or the Addenbooke’s Cognitive Assessment-​
III (ACE-​III). These require correction of extraneous influences
such as a quiet space, fewer interruptions, and the use of visual and
auditory aids. A brief attention test (e.g. counting down from 20 to
1) may help identify inattention due to delirium.
Insight into their condition
Insight is almost always absent in confused patients but this rarely
discriminates causes. Patients with severe depression are likely to
self-​blame for their situation, while patients with dementia may
make bland but frank denials of problems.
Physical assessment
The physical assessment of a patient presenting with confusion is
often difficult and may need to be opportunistic. A period of obser-
vation may show a slumped patient unable to sustain posture, or they
may be agitated and fidgety in the bed. Hands waving in the air, or
picking at the sheets are specific signs seen in delirium (floccilation).
If the patient is walking then observe the gait for signs of truncal
Box 26.3.1.2  Key points in the history of a patient presenting
with confusion
•	 What is patient’s baseline? (ADLs, cognition, personality)
•	 When did the change happen?
•	 Has any obvious factor led to this? (new drug/​operation/​change of
dwelling)
•	 Has there been a change in alertness/​attention span?
•	 Do they seem forgetful even when fully alert?
section 26  Psychiatric and drug-related disorders
6456
rigidity (stiffness), or frank Parkinsonism in vascular dementia or
dementia with Lewy bodies. Physical signs are listed in Box 26.3.1.3.
Temperature, blood pressure, heart rate, respiratory rate,
and oxygen saturation should be done to investigate for infec-
tion, or systemic inflammatory response. This is often blunted
in older people however. Blood tests for markers of infection
(white cell count, C-​reactive protein, or blood cultures) should
be performed.
Neurological examination
Neurological examination should focus on opthalmoplegias,
and focal neurological deficits such as unilateral limb weakness.
These suggest the presence of stroke, subdural haematoma, or a
Parkinson’s plus syndrome. Signs of upper limb rigidity or cog-​
wheeling may be present in cerebrovascular disease or in dementia
with Lewy bodies. CT brain imaging is rarely helpful in delirium,
but should be done in the context of focal neurological signs, recent
head injury, or use of oral anticoagulants. More detailed imaging
with MRI, functional imaging, or cerebrospinal fluid examination
may be indicated in cases where the diagnosis is unclear.
Cardiovascular, respiratory, and abdominal examination
These should focus on the assessment of potential sources of infec-
tion in the case of delirium. Abdominal examination should rule
out peritonism and focus on the possibility of constipation. A rectal
examination to look for faecal impaction may be appropriate. Chest
and abdominal X-​rays should be considered.
Urinary system
Urinary tract infection is overdiagnosed as a cause of delirium
in older people and routine urine dipstick testing is usually of no
value due to a low positive predictive value. Urinary incontin-
ence may be found in normal pressure hydrocephalus. A  palp-
able bladder from urinary retention should be excluded; bedside
bladder scanning can help. Blood tests should include renal func-
tion and electrolytes.
Musculoskeletal system
Care should be taken to examine for injuries or joint inflammation
as a cause of pain. Examine the hips to exclude fracture of the fem-
oral neck and have a low threshold to x-​ray the pelvis.
Management
The first priority in management is to keep the confused person safe.
In hospital this usually requires a quiet side room and often special
nursing attention.
Sequential assessments are always necessary in confused patients.
Rapid and potentially useful assessments include the Confusion
Assessment Method (CAM) or a brief cognitive assessment like
Abbreviated Mental Test (AMTS) or 4-​AT. The CAM helps focus on
the key clinical features of delirium—​rapid onset, fluctuating course,
inattention, disorganized thinking, and altered level of consciousness.
For delirium an urgent and vigorous search for the cause is re-
quired. As well as common causes such as infection, cerebral is-
chaemia and cardiac ischaemia it is important not to forget the effect
of prescribed medications and withdrawal from alcohol. Rapid reso-
lution of symptoms makes delirium the most likely diagnosis, and
no further action may be required.
However if the patient remains persistently cognitively impaired,
without fluctuation, in clear consciousness, then dementia must be
strongly suspected. Referral on to a memory clinic is likely to be re-
quired, and done according to local protocols.
A clinical picture dominated by agitation, psychomotor retard-
ation, gloominess, poor oral intake and passive resistance to care will
strongly suggest a severe depressive disorder and urgent referral to
psychiatric services is needed.
Conclusion
Patients presenting with confusion in general hospitals are at high
risk of having significant undiagnosed organic brain disorders, with
up to half of all cases of dementia being undiagnosed. The rate of
diagnosis could potentially be improved by systematic screening,
though potential problems include the high mortality of patients
who have been through the general hospital, and the high propor-
tion of false positive cases who will be subject to stressful and nega-
tive investigations for dementia.
Contrary to common belief, many cases of delirium do not re-
solve rapidly. Around 40% of general hospital cases of delirium are
unresolved at discharge and up to 20% of cases are unresolved after
six months. Finally, delirium is also a well-​established risk factor for
development of later dementia.
FURTHER READING
Inouye SK (2003). The Confusion Assessment Method (CAM): Training
manual and coding guide. Yale University School of Medicine, New
Haven, CT.
Sampson E, et al. (2009). Dementia in the acute hospital: Prospective
cohort study of prevalence and mortality. Br J Psychiatry, 195, 61–​6.
Cole MG (2010). Persistent delirium in older hospital inpatients. Curr
Opin Psychiatry, 23, 250–​4.
Bellelli G, et al. (2014). Validation of the 4AT, a new instrument for
rapid delirium screening: A study in 234 hospitalised older people.
Age Ageing, 43, 496–​502.
Gross AL, et al. (2012). Delirium and long-​term cognitive trajectory
among persons with dementia. Arch Int Med, 172, 1324–​31.
Box 26.3.1.3  Common physical signs that are important not
to miss in the confused patient
•	 Urinary retention, constipation
•	 Occult causes of pain
•	 Has there been a recent fall or injury?
•	 Are there signs of hip injury?
•	 Neurological signs
•	 Obvious ophthalmoplegia
•	 Obvious hemiplegia
•	 Physical signs of delirium
•	 Typical hand movements (aimless plucking at bed clothes, also
known as floccilation or tilmus)
•	 Tremor, dysgraphia

26.3.2 Self- harm 6457 Kate E.A. Saunders and Keit
26.3.2 Self- harm 6457 Kate E.A. Saunders and Keith Hawton
26.3.2  Self-harm
6457
26.3.2  Self-​harm
Kate E.A. Saunders and Keith Hawton
ESSENTIALS
Self-​harm is one of the commonest reasons people present to hos-
pital emergency departments and the most frequent form of self-​
harm is overdose. Most patients who self-​harm have an emotional
disturbance, commonly an adjustment or mood disorder, often in a
context of situational or relationship stresses, and personality difficul-
ties. Some have more severe psychiatric disorders. Intoxication with
alcohol is common.
All patients presenting with self-​harm require both a medical and
a psychiatric assessment. The latter should include an assessment
of problems, needs and suicide risk. Children require particularly
careful assessment. In assessing suicide risk, it should be noted that
the medical dangerousness of the act does not necessarily reflect the
intent, and that repeat self-​harm greatly increases the risk of eventual
suicide. Psychiatric management depends on the patient’s problems
and diagnosis. There is some evidence that brief psychological inter-
vention can decrease the risk of repeat self-​harm.
Introduction
Self-​harm is the term used in the United Kingdom (and much
of Europe) to describe intentional non​fatal self-​poisoning and
self-​injury, irrespective of motive. Self-​harm is a significant and
increasing problem in most developed (and some developing) coun-
tries. Two-​thirds of patients who self-​harm are under 35 years of age.
Self-​harm is rare in children but becomes more common in adoles-
cence. Self-​harm is more common in females and more common in
areas of socioeconomic deprivation.
Most patients seen in general hospitals for self-​harm have taken
overdoses. In the United Kingdom, the substances most frequently
involved are non​opioid analgesics, particularly paracetamol and
paracetamol-​containing compounds, and psychotropic agents, es-
pecially antidepressants and minor tranquillizers. Some patients
present with self-​injury, most commonly self-​cutting but sometimes
following more violent self-​harm such as hanging or jumping from
a height. In lower-​ and middle-​income countries, more toxic sub-
stances, such as pesticides, are often used for self-​poisoning (espe-
cially in rural areas), with consequent higher fatality rates.
Case examples
Case 1. An 18-​year-​old woman presents at 23.00 h on a Saturday
having taken a packet of paracetamol following an argument with
a boyfriend and while intoxicated with alcohol. She has presented
previously in similar scenarios. The history reveals a troubled up-
bringing with foster parents and ongoing difficulty with relation-
ships with others. Further assessment reveals fluctuating mood but
no depressive disorder. The assessment finds evidence of person-
ality problems and problem drinking. Case 2. A 60-​year-​old man
is admitted to hospital after attempted self-​hanging. He is divorced,
has lost his job, and is in debt. He left a suicide note. He has no pre-
vious episodes of self-​harm. Assessment reveals a severe depressive
disorder and a high suicide risk.
Relevant psychiatric disorders
Most who present to hospital following self-​harm will have a psy-
chiatric disorder, the most common being depression, anxiety
disorders, and personality difficulties and disorders. Adjustment
disorders to interpersonal problems and broken relationships (es-
pecially in the young), employment difficulties, legal and housing
problems, and alcohol and drug misuse are also common. Self-​harm
may also occur in the context of a psychotic illness such as schizo-
phrenia or bipolar disorder.
Assessment
Immediate assessment of risk
In addition to the immediate assessment of the medical conse-
quences of self-​harm, a brief and early assessment of the patient’s
psychiatric state and risk is essential. In particular, it is important
to know whether the patient has a serious psychiatric disorder (e.g.
psychosis or severe depression) and/​or is actively suicidal in order
to determine the need for urgent psychiatric attention. Risk may be
ongoing and dangerous tablets or other potential methods of self-​
harm (e.g. blades, ligatures) should be removed from the patient’s
possession.
Patients who self-​harm may leave hospital before a psychiatric
assessment can be completed. Such patients tend to have a his-
tory of substance abuse and previous self-​harm, and may exhibit
disturbed behaviour in hospital. Where a patient is thought to be
at serious risk and wanting to leave hospital, medical staff can (in
England and Wales at least) detain the patient under the Mental
Capacity Act until a psychiatric opinion can be obtained. Then, if
necessary, detention under the Mental Health Act can be arranged.
Refusal of medical treatment
Difficulty commonly arises when patients refuse potentially life-​
saving medical treatment. This problem is most common in those
who have poisoned themselves, such as with large overdoses of para-
cetamol, for which early treatment can prevent the development of
potentially fatal liver damage. The dilemma then is whether to in-
stigate medical treatment against a patient’s will. In most countries,
the issue is one of mental capacity. To show that patients have the
capacity to refuse treatment, they must:
•	 Be able to understand and retain information on the treatment
proposed, its indications, and its main benefits, as well as possible
risks and the consequences of non​treatment
•	 Be capable of weighing up the information in order to arrive at a
conclusion
•	 Be able to communicate this decision
Efforts should be made to optimize a patient’s capacity before con-
cluding that it is lacking. If a clinician instigates treatment against a
section 26  Psychiatric and drug-related disorders
6458
patient’s wishes in a patient who has capacity, then the clinician is
at risk of being accused of assault. Where the patient is judged to be
lacking capacity, essential medical treatment can be instigated (in
England and Wales) under the Mental Capacity Act. In situations of
dire emergency, most clinicians would choose to instigate essential
medical treatment to save the patient’s life and sort out legal issues
afterwards. Such understandable action is unlikely to lead to suc-
cessful litigation as long as the clinician is seen to act in the patient’s
best interest.
Psychiatric and social assessment
General hospital medical and nursing staff should be able to as-
sess the patient who has self-​harmed, but in many hospitals there
are specialist mental health teams who do this. The main topics to
be covered when interviewing the person who has self-​harmed are
listed in Box 26.3.2.1. A useful way of assessing the events and dif-
ficulties that preceded the act, the nature of the act, possible motiv-
ation, and suicidal intent, is to obtain a detailed account of the few
days leading up to the self-​harm. Whenever possible the patient’s
account should be supplemented with reports from informants such
as a partner, relatives, and friends and other involved in the patient’s
care, including their general practitioner.
Assessment of the motives or intentions underlying self-​harm
is based on the circumstances of the act, the patient’s account, that
of other informants, and deduction by the clinician. Common
motives or intentions for attempted self-​harm are shown in Box
26.3.2.2.
Suicidal intent (that is to say, the extent to which the patient
wished to die at the time of self-​harm) can usefully be assessed by
reviewing the circumstances of the act and the explanation given
by the patient and by relatives or friends. Factors suggesting high
suicidal intent are shown in Box 26.3.2.3. It is also important to take
account of what the patient and others say about the purpose of the
act. About one-​third of patients will say that they definitely wanted to
die, although in some cases the circumstances of the act will suggest
otherwise. However, there is a small but important group of patients
who will claim they did not wish to die when the circumstances sug-
gest high suicidal intent; such patients may be at increased risk of
repeated self-​harm, which has a high chance of being fatal. Scoring
systems can assist in the assessment of suicidal intent (e.g. the Beck
Suicide Intent Scale).
It is important to recognize that the objectively assessed risk to
life judged by the method used is a poor and potentially misleading
measure of the extent to which a patient wanted to die. Many pa-
tients have little idea about the relative dangers of substances taken
in overdose. Thus, a small overdose of a benzodiazepine hypnotic
or even an antibiotic may be a serious suicide attempt for some
patients, whereas a large overdose of a highly dangerous analgesic
might be taken with low intent by others. People in the medical and
allied health professions are an exception, and usually the danger of
their acts is a good measure of intent. Very dangerous self-​injuries
such as jumping from a height are usually associated with high sui-
cidal intent, but not always.
Estimation of the risk of repetition and of suicide following self-​
harm both short-​term and long-​term, is an important part of the
assessment. Factors associated with an increased risk of repeated
self-​harm and of suicide are shown in Table 26.3.2.1. However, it is
essential to recognize that such predictive measures are notoriously
imprecise. Patients with risk factors for repetition have a high risk
of repeating, but many who repeat—​possibly more than half—​have
few risk factors. The prediction of suicide is difficult, in part because
the risk of suicide is relatively low.
Assessment of protective factors is based on past behaviour under
stress and the patient’s account of whom they can turn to for sup-
port. It is important to assess whether the patient has difficulties in
problem-​solving, as these can be a target for therapy. The best evi-
dence for such difficulties will be a description of the methods used
to solve problems in the past. It is always important to determine
Box 26.3.2.1  Areas to be covered in the assessment of patients
who have self-​harmed
•	 Life events that preceded the act
•	 Motives for the act, including suicidal intent and other reasons
•	 Problems faced by the patient
•	 Psychiatric disorder
•	 Personality traits and disorder
•	 Alcohol and drug misuse
•	 Psychiatric treatment
•	 Previous self-​harm and its consequences
•	 Family and personal history
•	 Exposure to suicide/​self-​harm in friends and/​or the media (including
the Internet and social media)
•	 Current circumstances, such as:
•	 social (e.g. extent of social relationships)
•	 domestic (e.g. living alone or with others)
•	 occupation (e.g. whether employed)
•	 Psychiatric history, including previous suicide attempts
•	 Risk of a further self-​harm
•	 Risk of suicide
•	 Coping resources and supports
Box 26.3.2.2  Common motives or intentions for self-​harm
•	 To die
•	 To escape from an unbearable situation
•	 To get relief from a distressed state of mind
•	 To change the behaviour of others
•	 To show desperation to others
•	 To get back at other people/​make them feel guilty
•	 To get help
Box 26.3.2.3  Factors suggesting high suicidal intent
•	 Act carried out in isolation
•	 Act timed so that intervention unlikely
•	 Precautions taken to avoid discovery
•	 Preparations made in anticipation of death (e.g. making a will, organ-
izing insurance)
•	 Preparations made for the act (e.g. purchasing means, saving up
tablets)
•	 Communicating intent to others beforehand
•	 Extensive premeditation
•	 Leaving a note
•	 Not alerting potential helpers after the act
26.3.2  Self-harm
6459
whether current problem-​solving is impaired by depression or other
psychiatric disorder.
Management
The management of self-​harm will depend in part on the medical
and psychiatric diagnoses. However, there are general principles
that apply to the psychological management of all patients.
Some patients who have self-​harmed appear ambivalent about ac-
cepting help, or even frankly dismissive of it. Clinicians may have to
work hard in some cases to explain to patients how treatment might
be of benefit to them.
The assessment procedure can itself be therapeutic. It may provide
patients with a first opportunity to discuss their difficulties with a
clinician. Joint interviews with family members can improve com-
munication. The psychosocial assessment probably reduces the like-
lihood of repetition of self-​harm.
Some patients thought to be at high risk of suicide refuse psy-
chiatric treatment when this is judged essential. Their subsequent
management depends on whether the patient is suffering, or likely
to be suffering, from a mental illness that necessitates hospital
assessment and/​or treatment. In most countries, if a patient is
thought to be at serious risk or seriously mentally ill, emergency
department staff would be judged to be acting reasonably if they
held the patient in the department until a psychiatric opinion
could be obtained.
Major psychiatric disorders should receive appropriate treatment.
Caution is needed where there is ongoing risk of self-​poisoning with
consideration given to the toxicity of the treatment and the amount
prescribed. The evidence that simple interventions reduce the risk of
repeated self-​harm is not strong, but there is increasing evidence for
the efficacy of psychological treatments, especially brief cognitive
behavioural therapy, including for reducing depression, hopeless-
ness, and suicidal ideation. Furthermore, intensive and prolonged
psychological therapy (dialectical behavioural therapy) can re-
duce the frequency of self-​harm in patients with a history of mul-
tiple acts of self-​harm and borderline personality disorder. Contact
interventions such as sending postcards to patients at regular inter-
vals following self-​harm may reduce repetition where community
psychiatric services are minimal or absent. Most evidence for spe-
cific interventions following self-​harm comes from studies in adults
and far less is known about the benefit of intervention for children
and adolescents or older adults.
The assessment of patients who have engaged in self-​harm is re-
garded by some physicians as primarily the responsibility of psy-
chiatrists. However, it has been found that nurses, social workers,
and other clinicians can assess these patients reliably, make ef-
fective aftercare arrangements, and provide therapy. Staff of what-
ever discipline should have the experience and skill to manage
patients with emotional and psychiatric disorders, and have been
trained in the assessment and treatment of patients who have self-​
harmed. They also require supervision and support from senior
psychiatrists, especially when managing patients with severe psy-
chiatric disorders and where compulsory admission to hospital
may be required.
Outcome
Self-​harm is often repeated; 12–​25% of people repeat the act within a
year. In the United Kingdom, around 1% will die by suicide within a
year and 3–​5% within 8–​10 years. More than half of people dying by
suicide have a prior history of self-​harm. In older patients, the risk
of suicide is higher. Self-​harm is also associated with physical illness
as well increased mortality from natural causes, especially alcohol-​
related disorders.
Specific subgroups of patients
Alcohol and drug abusers
Many patients who self-​harm have problems related to alcohol and
drug abuse, and these factors—​especially alcohol abuse—​increase
the risk of both repetition and suicide. Screening for substance abuse
should therefore be part of self-​harm assessment.
Patients with personality disorders
Personality difficulty or disorder is a common primary or comorbid
diagnosis in patients who self-​harm. Repetition of self-​harm is very
common in this group and their suicide risk is significant. At pre-
sent, there are no licensed medications for personality disorder and
admission to inpatient psychiatric wards is only advised for crises
where all community options have been exhausted. Some areas
have designated services for people with severe personality dis-
orders. For those who repeat very frequently it can be useful to have
a pre-​agreed approach to management in order to ensure safe and
consistent care.
Children and young adolescents
It is usually advisable that children and young adolescents who
self-​harm be admitted to hospital as they may require particularly
complex and often prolonged assessment, including interviews with
their families and the possible involvement of community statutory
services (e.g. social services).
Table 26.3.2.1  Factors associated with an increased risk of a repeat
self-​harm and of suicide
Self-​harm
Suicide
•	 Previous episodes of self-​harm
•	 Personality disorder
•	 Alcohol or drug abuse
•	 Previous psychiatric treatment
•	 Unemployment
•	 Socio-economic deprivation
•	 Criminal record
•	 History of violence
•	 Single, divorced, or separated
•	 Older age
•	 Male gender
•	 Unemployed or retired
•	 Separated, divorced, or widowed
•	 Living alone
•	 Poor physical health
•	 Psychiatric disorder (particularly
depression, alcoholism,
schizophrenia, and personality
disorder)
•	 High suicidal intent in current
episode
•	 Violent method involved in self-​
harm (e.g. attempted hanging,
jumping)
•	 Leaving a suicide note
•	 Previous self-​harm, especially
multiple episodes

26.3.3 Medically unexplained symptoms 6460 Michael
26.3.3 Medically unexplained symptoms 6460 Michael Sharpe
section 26  Psychiatric and drug-related disorders
6460
Elderly patients
Self-​harm in older patients, while much less common than in younger
people, is often of high suicidal intent and carries a high risk of sub-
sequent suicide, hence routine admission to a medical bed is often
recommended for this group. The involvement of the older adult
psychiatry service (if one exists) is important in planning aftercare.
FURTHER READING
Carroll R, Metcalfe C, Gunnell D (2014). Hospital presenting self-​
harm and risk of fatal and non-​fatal repetition: systematic review
and meta-​analysis. PLoS One, 9, e89944
Hawton K, Saunders KEA, O’Connor R (2012). Self-​harm and suicide
in adolescents. Lancet, 379, 2373–​82.
Hawton K, et al. (2016). Psychosocial interventions for self-​harm in
adults. Cochrane Database Syst Rev, 5, CD012189.
National Collaborating Centre for Mental Health (2004). Self-​
harm:  the short-​term physical and psychological management and
secondary prevention of self-​harm in primary and secondary care (full
guideline), Clinical Guideline 16. National Institute for Health and
Clinical Excellence, London.
National Institute for Health and Care Excellence (2011). Self-​harm: the
longer-​term management (full guideline), Clinical Guideline 133.
National Institute for Health and Care Excellence, Manchester.
26.3.3  Medically unexplained
symptoms
Michael Sharpe
ESSENTIALS
Physical symptoms are not always associated with disease. In sec-
ondary medical care as many as a third of patients present with symp-
toms unexplained by disease. Such ‘medically unexplained symptoms’
pose a challenge for clinical services that focus on identifying and
treating disease. The principles of effective management are to: (a)
avoid overinvestigation and giving speculative treatment for disease,
(b) take a positive approach with the patient, accepting the reality of
the symptoms while explaining clearly that they do not indicate dis-
ease, (c) identify and provide treatment for associated depression and
anxiety disorders, (d) refer for psychiatric or psychological treatment
when required. Complex cases with multiple persistent medically un-
explained symptoms are at particular risk of iatrogenic harm and re-
quire active multidisciplinary management. Psychological treatments
such as cognitive behaviour therapy may be effective.
Introduction
Patients generally present to doctors with symptoms for which the
doctor then seeks evidence of disease. If bodily disease is found it is
typically assumed that the symptoms were an expression of that disease;
to put it another way, the disease ‘explains’ the symptoms. If no disease
is found, the symptoms may be regarded as ‘medically unexplained’.
While labelling symptoms as ‘medically unexplained’ may have
some practical use in limiting excessive investigation and inappro-
priate treatment, it also has limitations. First, it may be used to imply
that only symptoms associated with objectively identifiable physical
disease are real, whereas all symptoms are subjective phenomena
and always real to the sufferer. Second, it assumes that medicine is
only concerned with bodily disease whereas the many physiological,
psychological, and social factors that contribute to the production of
symptoms are also legitimate areas of medical interest.
Medically unexplained symptoms (MUS) are common. They
account for a substantial proportion of the work of most doctors.
How explained a symptom is by disease may be regarded as being on
a continuum from ‘not at all explained’ to ‘completely explained’, with
a gradation in between. When defined as symptoms associated with
but inadequately explained by disease, they account for approximately
one-​third of new medical outpatient consultations and when defined
as symptoms in the absence of any disease, about 1 in 10 consultations.
Although sometimes dismissed as merely the ‘worried well’, pa-
tients with medically unexplained symptoms often suffer even
greater disability and distress than patients whose symptoms are ex-
plained by disease. They are also expensive to the healthcare system
because they may receive extensive but unproductive investigation
and treatment without benefit. Understandably, doctors often find
patients with medically unexplained symptoms ‘difficult to help’.
Given the size and importance of this clinical problem, it is sur-
prising how relatively neglected it is in textbooks.
Common scenarios
Almost any symptom can remain medically unexplained, even after
exhaustive medical assessment. Common examples include pain
(including back pain, chest pain, abdominal pain, and headache);
fatigue and weakness; dizziness; ‘fits’ and funny turns. Symptoms
can present singly, but are often multiple.
Case 1. A typical presentation.
A young woman has attended her primary care physician repeat-
edly with headache. The history reveals nothing specific about
the headache but she is concerned that she has a brain tumour.
Examination is normal but she is anxious. She requests a brain
scan.
Case 2. A complex presentation.
A middle-​aged woman, referred to as a ‘heart-​sink’ patient by her
primary care physician, is referred to a general medical outpatient
service with dizziness, bloating of her stomach, and generalized
weakness. She has extensive medical notes documenting her pre-
vious presentations with a range of symptoms including pain in
various places, irritable bowel, menstrual problems, and transient
loss of sight. She has had many investigations, as well as a hyster-
ectomy and three laparotomies. She is taking a long list of pre-
scribed medications, including oral opioids. Review of her notes
reveals various diagnoses including endometriosis, none of which
adequately explain the presentation. Examination reveals only
several operation scars.
26.3.3  Medically unexplained symptoms
6461
Differential diagnosis
The main medical differential diagnosis for medically unexplained
symptoms is serious disease. Diagnostic difficulties are likely to
occur with unusual presentations of common diseases and with rare
diseases. While the risk of missing the diagnosis of serious disease
is clearly an appropriate concern, the evidence indicates that once a
patient has been carefully assessed, the later emergence of a ‘missed’
disease is uncommon. What is more common is the failure to ad-
dress the differential diagnosis.
Functional somatic syndromes
There are specialty specific syndrome names to describe patients
with medically unexplained symptoms (Table 26.3.3.1). These are
based on the bodily system the physical symptoms are presumed to
relate to and the associated medical specialty. These are not alterna-
tives to the psychiatric diagnoses listed next, but rather provide a
parallel descriptive system that can be of pragmatic descriptive value.
Psychiatric diagnoses
There are several psychiatric diagnoses relevant to patients with
medically unexplained symptoms (Table 26.3.3.2). These are based
on the patient’s psychological rather than physical symptoms and are
not therefore specific to bodily system or medical specialty, and they
may have important implications for treatment.
Depression and anxiety
Depression and anxiety disorders have physical as well as psycho-
logical symptoms. Fatigue, weight loss, and pain are common in
depression. Chronic tension, bodily aches, and poor sleep suggest
chronic anxiety. Severe episodic symptoms such as chest pain, dizzi-
ness, and breathlessness suggest panic attacks.
Health anxiety disorder
When the patient has severe anxiety focused specifically on the
fear of possible sinister causes for their symptoms, the appropriate
diagnosis might be health anxiety disorder (previously called hypo-
chondriasis). Such patients may check their body many times a day,
repeatedly seek reassurance from the physician and ask for repeated
investigations.
Somatic symptom disorder
When the patient does not have a depressive or anxiety disorder,
a diagnosis of somatic symptom disorder might be appropriate.
This disorder was previously called somatoform disorder. It may be
simple, with concern about a few symptoms, or complex, with mul-
tiple persistent symptoms and high use of healthcare.
Functional neurological disorder
Patients whose symptoms include loss of a function such as move-
ment of a limb or loss of vision that is not explained by disease may
have a functional neurological disorder. This was previously called
conversion disorder or conversion hysteria.
Psychosis
Occasionally the physician may encounter a patient whose phys-
ical symptoms are part of a psychosis. The clue to the psychotic
nature of the presentation may be the patient’s bizarre descrip-
tion of and explanation for the symptom; for example, a shifting
burning feeling in the skin resulting from radio waves beamed by
persecutors.
Factitious disorder and malingering
Patients occasionally deliberately feign or simulate symptoms. If the
apparent aim of this behaviour is to obtain medical attention and
treatment the diagnosis given is that of ‘factitious disorder’ (which is
preferable to the eponym Munchausen’s syndrome used to describe
severe wandering cases of factitious disorder). Sufferers are usually
female, often in caring roles, and have histories of childhood mal-
treatment and illness.
Factitious disorder should be distinguished from malingering,
which is not a psychiatric disorder but a term used to refer to a be-
haviour of deliberate deception in order to obtain a desired aim such
as financial compensation or release from prison.
Assessment
The conclusion that a patient’s symptoms are medically unexplained
may be arrived at only after history, examination, and investiga-
tion. Sometimes the history alone suggests that the symptoms de-
scribed are not those of disease. While misdiagnosis of medically
unexplained symptoms is relatively uncommon, it is more likely to
occur when the patient looks ‘psychiatric’ or has a history of mental
illness.
Table 26.3.3.1  Medical specialty specific names for medically
unexplained syndromes
Syndrome
Specialty
Irritable bowel syndrome, non​ulcer dyspepsia
Gastroenterology
Premenstrual syndrome, chronic pelvic pain
Gynaecology
Fibromyalgia
Rheumatology
Atypical or non​cardiac chest pain
Cardiology
Hyperventilation
Respiratory medicine
Chronic (post-​viral) fatigue syndrome
Infectious diseases
Tension headache, non​epileptic attacks
Neurology
Table 26.3.3.2  Psychiatric diagnoses for medically unexplained
symptoms
Diagnosis
Notes
Depressive disorder
Anxiety and panic disorders
Somatic symptom disorder
Previously called somatoform
disorder or somatization disorder
Health anxiety disorder
Previously called hypochondriasis
Conversion disorder
Also called functional neurological
disorder
Psychosis
With somatic delusions and
hallucinations
Factitious disorder

26.3.4 Low mood 6462 Jane Walker
26.3.4 Low mood 6462 Jane Walker
section 26  Psychiatric and drug-related disorders
6462
Physical examination
Even if symptoms are suspected to be medically unexplained, it is
useful to physically examine the patient. This may not only reveal
unsuspected clinical signs but also helps to reassure the patient that
their complaints have been taken seriously and properly assessed.
Investigation
Investigations are important. However, a balance must be struck be-
tween the risk of missing disease and the potential iatrogenic psy-
chological harm in increasing the patient’s fear of disease that can
result from excessive and unnecessary investigation.
Asking about fears and beliefs
It is particularly important to find out what the patent thinks or fears
is wrong with them. This can reveal why they have presented (e.g. ‘I
am worried that it could be cancer’). In some cases anxiety about a
specific disease may be the main reason for presentation. If this is
severe and persistent, the diagnosis may be one of health anxiety
(hypochondriasis). If bizarre and fixed, it may indicate a delusion.
Asking about psychological symptoms
Asking about the additional psychological symptoms may indicate
one of the treatable psychiatric diagnoses listed in the differential
just mentioned. However, care must be taken with asking about psy-
chological symptoms such as depressed and anxious mood as this
may give the patient the impression that their concerns about phys-
ical disease have been prematurely dismissed. Consequently, such
enquiry is often best done only after taking a history of the physical
symptoms when they can be asked about as understandable conse-
quences of the symptoms themselves.
Management
The management will depend on the diagnosis, but there are general
principles:
•	 First, patients need to know that the doctor believes them.
Symptoms are subjective phenomena and the lack of disease does
not mean that their suffering is in some way inauthentic. It often
helps to spell this out: ‘I appreciate that you have had some very
troublesome and distressing symptoms’.
•	 Second, they need a clear message that no serious disease has been
found. However, this needs to be worded carefully. Simply saying
‘there is nothing wrong’ can be heard by the patient as being dismis-
sive of their symptoms. Rather it may be better to say: ‘I am pleased
to be able to tell you that, despite how troubling these symptoms
have been, they do not indicate a serious medical disease.’
•	 Third, patients need a positive plan. This may include follow up
from the physician, referral to a colleague, or a recommenda-
tion to the primary care physician. This can be explained as fol-
lows: ‘I do hope that your symptoms will improve. They often do.
However, in case they do not I will see you again/​ask your primary
care physician to review you in a month’s time to review the need
for treatment’. The specific treatment will depend on the diagnosis.
When there is evidence of a depressive or anxiety disorder, this
can be explained as follows: ‘Having physical symptoms can lead to
depression and anxiety; these in turn can make the symptoms worse—​
a vicious circle. I suggest that we treat the depression/​anxiety and see
if the physical symptoms improve. In my experience they often do.’
When the diagnosis is somatic symptom disorder, so-​called ‘anti-
depressant drugs’ and specific forms of cognitive behaviour therapy
(CBT) can be helpful. When available there are specific services and
teams, for example, pain teams and liaison psychiatric services for
patients with severe and chronic symptoms. Complex cases may
need case conferences and a multidisciplinary management plan.
Prognosis
Most medically unexplained symptoms presenting to primary care
resolve, but those who are referred to secondary care are more likely
to persist. These patients are at risk of iatrogenic harm from exces-
sive investigation and unhelpful medical and surgical treatment.
FURTHER READING
Creed F, et al. (2010). Is there a better term than ‘medically unex-
plained symptoms’? J Psychosom Res, 68, 5–​8.
Hatcher S, Arrol B (2008). Assessment and management of medically
unexplained symptoms. BMJ, 336, 1124–​8.
Sharpe M, Carson A (2001). ‘Unexplained’ somatic symptoms, func-
tional syndromes, and somatization: do we need a paradigm shift?
Ann Int Med, 134, 926–​30.
Wessely S, Nimnuan C, Sharpe M (1999). Functional somatic syn-
dromes: one or many? Lancet, 354, 936.
26.3.4  Low mood
Jane Walker
ESSENTIALS
Low mood is a very common symptom that is often considered a
normal, understandable reaction to serious, disabling, or disfiguring
illnesses or treatment. While low mood may indeed be part of the
adjustment to adverse circumstances, it may also be the presen-
tation of serious psychiatric and medical illnesses requiring active
treatment. The most common of these is major depressive disorder,
which is a complicating illness in about 10% of patients with chronic
medical conditions. Simple questioning can clarify the diagnosis, but
sometimes a more detailed psychiatric and medical assessment is
required so that the appropriate treatment can be provided.
Introduction
Low mood is a common symptom in patients with medical illnesses.
Despite its prevalence and negative effects, low mood is often over-
looked in the medically ill. There are several reasons for this. Patients
26.3.4  Low mood
6463
often assume that it is normal to feel low in the context of a medical
illness; they may not wish to burden their doctor with something
they consider untreatable; and they may believe that admitting to
low mood might be taken as a sign of ‘not coping’, leading to a dis-
continuation of their treatment. Clinicians, for their part, often lack
confidence in how to assess low mood.
Common scenarios
Case 1. A 68-​year-​old, previously fit, man presented to his pri-
mary care physician with shortness of breath on exertion.
Following investigations he was diagnosed with metastatic lung
adenocarcinoma with a prognosis of approximately 12 months.
At his chemotherapy appointment he described losing interest in
golf and DIY, which he was still physically capable of doing. He felt
restless and unable to look forward to anything. The differential
diagnosis of the low mood includes adjustment disorder, side ef-
fects of chemotherapy, major depressive disorder, and developing
organic brain syndrome.
Case 2. An 85-​year-​old woman was admitted to a medical ward with
loss of appetite, fatigue, and urinary incontinence. She appeared
withdrawn, refused medications, and was reluctant to get out of bed.
She responded only minimally during attempts to converse with her.
The differential diagnosis of the low mood includes hypoactive de-
lirium, dementia, and severe major depressive disorder.
Differential diagnosis
While the most obvious psychiatric disorder associated with low
mood is major depression, other diagnoses must be considered.
Major depression is characterized by pervasive low mood that has
persisted for at least two weeks, loss of enjoyment, or motivation, and
other symptoms including changes in sleep and appetite. Depression
may be a consequence of medical illness, a cause of it, or the two may
coexist as a result of common aetiological factors. Occasionally fur-
ther assessment will indicate a history of episodes of elevated mood
or mania, suggesting a bipolar mood disorder.
The main differential diagnosis is that of adjustment disorder. This
is a diagnosis used to describe the time-limited psychological symp-
toms, including low mood, that occur during adjustment to a diffi-
culty such as a new and unpleasant illness. As the term suggests, the
symptoms only last while the stressor is present and are neither per-
sistent nor severe enough to justify a diagnosis of major depression.
However, adjustment disorders can develop into depressive illness
and monitoring of the patient’s mood is important.
Other psychiatric disorders to bear in mind in the differential
diagnosis of low mood are alcohol and substance misuse, dementia,
and delirium (particularly hypoactive delirium).
In addition to the psychiatric disorders just described, several
other medical illnesses and their treatments can cause low mood
and should be considered when the symptom is interfering with the
patient’s ability to function (Box 26.3.4.1). The most common of
these is thyroid dysfunction, in particular hypothyroidism.
Some pharmacological treatments have also been associated with
low mood (Box 26.3.4.2).
Assessment
Assessment should focus on: (a) evaluating the nature and severity
of the low mood; (b) determining the presence or absence of psychi-
atric disorders; (c) considering other possible medical causes.
Starting the conversation
Patients may not divulge that they are feeling low, just as they may
not report being in pain unless prompted to do so. The clinician
therefore needs to have a few stock phrases that they can use to open
a conversation about low mood. Open questions such as ‘how have
you been feeling in yourself/​your spirits/​your mood?’ can be a good
way to begin. Patients may, however, be unfamiliar with questions
about their emotional well-​being and respond with a description of
their physical health. In this instance, a closed question about the
presence of low mood may be required, for example, ‘when patients
have this medical problem it can often make them feel down or low,
have you found that?’
Assessing the nature and severity of low mood
It is important to assess whether the patient’s low mood is persistent
and how severe it is. Having established that the patient feels low
or down some of the time, the clinician can go on to ask, ‘what is
that like for you?’ or ‘what does it feel like when you get low?’ Using
the patient’s own words for their feelings, even if these are not part
Box 26.3.4.1  Common differential diagnoses for patients
presenting with low mood
Major depression (which may be part of bipolar disorder)
Chronic depression
Adjustment disorder
Alcohol and substance misuse
Delirium
Dementia
Side effects of medication
Direct result of medical illness (e.g. hypothyroidism, brain injury)
Personality disorder
Box 26.3.4.2  Commonly prescribed medications that have
been reported to cause low mood
ACE inhibitors
Anticonvulsants
Methyldopa
Thiazides
Amphotericin
Ethionamide
Metronidazole
Some anticancer drugs
β-blockers
Calcium channel blockers
Corticosteroids
Oestrogens
Interferon
Isotretinoin
Metoclopramide
Indomethacin
Statins
Sedative hypnotics
section 26  Psychiatric and drug-related disorders
6464
of the clinician’s usual vocabulary, can make the assessment more
comfortable for the patient, who will often be explaining how they
feel for the first time. How persistent the low mood is can be estab-
lished by asking how long the periods of low mood last; in a de-
pressive disorder, the mood will be low most of the time. Severity
can be assessed using simple questions such as ‘how bad does it get
when you feel like this?’ and by asking the patient how their life has
been affected by their low mood—​have they stopped doing things
they usually would, or stopped enjoying them. Patient-​rated ques-
tionnaires, such as the PHQ-​9, can be used to identify patients with
probable major depression or to monitor the severity of a patient’s
low mood, but a questionnaire is never a proper substitute for a clin-
ical assessment.
Assessing mood when communication is difficult
Assessing whether patients have low mood and (if so) how severe
that is usually involves a conversation, as described previously.
However, there are situations when this can be difficult to achieve,
for example, when patients are unable to speak due to a neuro-
logical disorder, or when their cognitive impairment prevents
them from communicating verbally. In these cases, observation of
the patient’s appearance and behaviour is essential. The clinician’s
observations should be supplemented with information from a
relative, friend, carer, or the patient’s usual clinician. Behaviour
such as poor eye contact, tearfulness, and lack of interest in per-
sonal appearance suggest a diagnosis of depression, whereas
fluctuating consciousness and a fearful appearance may be indi-
cators of delirium.
Suicide risk assessment
If the patient has severe low mood it is necessary to also ask ques-
tions about suicidal thoughts. There is no evidence that encouraging
patients to talk about such thoughts increases the risk of suicide.
Suicide risk assessment should start with a question about the
patient’s desire for death, for example, ‘sometimes when people feel
low like this, they can start to think that they might be better off dead;
do you ever feel like that?’ If the patient denies any wish to die, the as-
sessment can stop. However if they agree that, at times they wish they
were not alive, the clinician should go on to enquire about thoughts
of actively ending their life. An affirmative answer to this question
should lead to further enquiry to establish the likelihood of suicidal
actions and the factors that may reduce the patient’s risk of suicide.
Management
The management of low mood depends on the cause. Antidepressant
medication, for example, is useful when the patient has major de-
pression but there is little evidence for its value in patients with
simple low mood. Patients should not be subjected to the potential
adverse effects of such drugs if the chance of benefitting is low. There
are, however, strategies that may be useful for low mood whatever
its cause, such as increasing activity, social engagement, and talking
treatment.
FURTHER READING
Allan C, Ebmeier K (2013). Review of treatment for late-​life depres-
sion. BJPsych Advances, 19, 302–​9.
Gilbody S, Sheldon T, Wessely S (2006). Should we screen for depres-
sion? Br Med J, 332, 1027–​30.
Simon GE, Von Korff M (2006). Medical co-​morbidity and validity of
DSM-​IV depression criteria. Psychol Med, 36, 27–​36.

26.4 Psychiatric treatments in the medically ill 6
26.4 Psychiatric treatments in the medically ill 6465 26.4.1 Psychopharmacology in medical practice 6465 Philip J. Cowen
CONTENTS
26.4.1	 Psychopharmacology in medical practice  6465
Philip J. Cowen
26.4.2	 Psychological treatments  6470
Michael Sharpe and Simon Wessely
26.4.1  Psychopharmacology in
medical practice
Philip J. Cowen
ESSENTIALS
Drugs intended to treat psychiatric disorders are referred to as psy-
chotropic drugs. The main categories are antidepressants, mood
stabilizing drugs, antipsychotic drugs, and antianxiety drugs.
These drugs are widely used in medical practice and most clin-
icians are likely to have under their care several patients receiving
treatment with them. Practitioners therefore need to have an under-
standing of both the uses and unwanted effects of psychotropic
drugs, and particularly of (1) their interactions with drugs used to treat
other medical conditions, (2) characteristic abstinence syndromes
that can occur with sudden discontinuation of antidepressants (par-
ticularly selective serotonin reuptake inhibitors and venlafaxine) and
anxiolytics.
Introduction
Psychotropic drugs are widely used in medical practice and most
clinicians are likely to have under their care several patients re-
ceiving treatment with this type of medication (Table 26.4.1.1).
Most psychotropic drugs are prescribed for the treatment of
depressive or anxiety disorders, reflecting the frequency of these
conditions in both primary care and general hospital settings.
Similarly, while the principal use of antipsychotic drugs is in the
treatment of schizophrenia, such agents are also used in general
hospitals in the management of the organic psychoses such as de-
lirium and dementia. Finally, while treatment with mood stabilizing
drugs, such as lithium, is generally initiated by psychiatrists, patients
receiving long-​term treatment with these agents may require treat-
ment for coexisting medical conditions, consequently knowledge of
the effects of lithium on different body systems and its liability to
produce adverse drug interactions will be required.
For many psychiatric conditions, particularly anxiety and de-
pressive disorders, psychological treatments are often as effective as
psychotropic drugs and may have other advantages. Hence, if appro-
priate psychological treatments are available, they should be con-
sidered as an alternative to, or addition to, drug therapy.
Special considerations
Overdose
Patients may present to medical services with the effects of delib-
erate or accidental overdose of psychotropic drugs. Consequently,
26.4
Psychiatric treatments in
the medically ill
Table 26.4.1.1  Classification of clinical psychotropic drugs
Name
Examples of agents
Indications
Antipsychotic
Haloperidol
Quetiapine
Risperidone
Acute treatment of
schizophrenia and mania,
prophylaxis of schizophrenia
Antidepressant
Fluoxetine
Venlafaxine
Mirtazapine
Major depression (acute
treatment and prophylaxis),
anxiety disorders, obsessive–​
compulsive disorder (SSRIs)
Mood stabilizer
Lithium
Valproate
Acute treatment of mania,
prophylaxis of recurrent
mood disorder
Anxiolytic
Diazepam
Lorazepam
Short-​term relief of anxiety
symptoms
Hypnotic
Temazepam
Zopiclone
Zolpidem
Insomnia
section 26  Psychiatric and drug-related disorders
6466
when prescribing psychotropic drugs, particularly for depressed pa-
tients, the risk of overdose should always be considered. If such a
risk is present, the practitioner should: (1) ensure that medication
is dispensed in small amounts; (2) consider asking a close relative to
supervise the medication; (3) use a relatively non​toxic drug, if this
is available.
Pharmacokinetic factors
Most psychotropic drugs are highly lipophilic and are well absorbed
from the gastrointestinal tract. They are then metabolized by the
liver to water-​soluble derivatives that are in turn eliminated by the
kidneys, hence the drug half-​life will be prolonged in patients with
hepatic or renal impairment and in older patients. When psycho-
tropic medication is added to another drug treatment the possibility
of drug interactions must be considered. For example, some se-
lective serotonin reuptake inhibitors (SSRIs) are potent inhibitors of
hepatic cytochrome P450 enzymes and can thereby increase plasma
levels of drugs such as warfarin.
Withdrawal of psychotropic medication
Characteristic abstinence syndromes occur with sudden discon-
tinuation of antidepressants (particularly SSRIs and venlafaxine)
and anxiolytics. The main symptoms are:
•	 Sleep disturbance—​insomnia, nightmares
•	 Mood symptoms—​irritability, anxiety, emotional lability
•	 Gastrointestinal symptoms—​nausea, diarrhoea
•	 Sensory—​electric shock sensations, light-​headedness, vertigo
•	 Somatic—​headache, lethargy, sweating
The sudden discontinuation of lithium can provoke a ‘rebound’
mania in bipolar patients. It is therefore prudent to withdraw psy-
chotropic drugs slowly whenever possible. It is also important to be
able to distinguish withdrawal syndromes from a relapse of the dis-
order being treated.
Compliance and concordance with treatment
Compliance with the prescribed drug regimen is an even greater
problem with psychotropic drugs than it is in general therapeutics.
Psychoactive drugs frequently have unpleasant side effects. These
may be experienced early in treatment and before a therapeutic re-
sponse is evident. Furthermore, patients may not see the need for
treatment or believe that it can help them. Consequently, the suc-
cessful and safe use of medication requires a collaborative relation-
ship between patient and doctor. The term ‘concordance’ may be
preferred to ‘compliance’, which carries the implicit assumption that
the patient’s task is to obey instructions. It is therefore important to
understand the patient’s view of their illness as well as of its treat-
ment. Careful explanation of the likely benefits of treatment and
what to expect, accompanied by written information, can help to
ensure that the drugs you prescribe are actually taken.
Antidepressant drugs
All antidepressant drugs in current use increase the activity of sero-
tonin (5-​hydroxytryptamine, 5-​HT) and/​or noradrenergic neurons
in the central nervous system (CNS) through one mechanism
or another. The pharmacological actions of both noradrenaline
(norepinephrine) and 5-​HT in the synapse are terminated by spe-
cific reuptake pumps that draw these neurotransmitters back into
the presynaptic nerve ending. Most antidepressants potentiate the
action of 5-​HT and noradrenaline by blocking this reuptake process.
Selective serotonin reuptake inhibitors (SSRIs)
The actions of SSRIs are confined to blockade of the reuptake of 5-​
hydroxytryptamine (5-​HT) and their use is associated with a sus-
tained increase in brain 5-​HT neurotransmission.
Most commonly used SSRIs
These are citalopram, escitalopram, fluoxetine, paroxetine, and
sertraline.
Indications and use
SSRIs are now first-​line treatment for moderate to severe depres-
sion. They are better tolerated than tricyclic antidepressants, less
cardiotoxic, and are relatively safe in overdose. There are few im-
portant therapeutic differences between them. If treatment is suc-
cessful, it is usual to continue the antidepressant for at least 6 months
(so-​called continuation therapy). This reduces the risk of early relapse
by about half. Some patients with recurrent depressive illness re-
quire long-​term ‘maintenance’ treatment with antidepressant drugs.
Adverse effects
The main adverse effects of SSRIs are shown in Table 26.4.1.2.
SSRIs can cause activation and agitation early in treatment and
there has been controversy as to whether this might be associated
with an increased risk of suicidal behaviour. There is some evidence
for this in young people and, with the exception of fluoxetine, SSRIs
are contraindicated in the treatment of depression in patients less
than 18 years old. The evidence for a pro-​suicidal effect of SSRIs in
adults is more equivocal; at a population level, some studies even
show a decreased suicide rate correlating with SSRI prescription.
However, it is likely that the initiation of antidepressant drug treat-
ment of any kind is associated with some increased risk of self-​harm
Table 26.4.1.2  Newer antidepressants and their adverse effects
Drug
Mechanism
Adverse effects
SSRIs
5-​HT reuptake blockade
Nausea, insomnia, headache,
anxiety, rash, sweating,
sexual dysfunction, low
sodium state, extrapyramidal
movement disorders (rare),
seizure (rare)
Venlafaxine,
duloxetine
5-​HT and noradrenaline
reuptake blockade
Nausea, headache,
insomnia, sweating, anxiety,
hypertension, sexual
dysfunction, seizure (rare),
overdose toxicity (venlafaxine)
Trazodone
5-​HT2-​receptor antagonism
and α1-​adrenoceptor
blockade
Sedation, dizziness, nausea,
postural hypotension,
priapism (rare), cardiac
arrhythmias (rare), seizure
(rare)
Mirtazapine
5-​HT2/​α2-​adrenoceptor
agonist
Sedation, weight gain,
abnormal liver function tests,
reversible agranulocytosis
(rare), seizure (rare)
26.4.1  Psychopharmacology in medical practice
6467
in the first weeks of treatment. Depressed patients should there-
fore be carefully monitored in the days after starting antidepressant
medication and that medication should be prescribed in limited
amounts.
Drug interactions
SSRIs, with the exception of citalopram and escitalopram, slow the
metabolism of numerous other drugs including warfarin, theophyl-
line, anticonvulsants, antipsychotics, and tricyclic antidepressants.
Dangerous interactions, characterized by 5-​HT neurotoxicity, have
been reported between SSRIs and monoamine oxidase inhibi-
tors. SSRIs may also produce 5-​HT toxicity in combination with
lithium, and with some medical drugs such as tramadol, linezolid,
and triptans. SSRIs increase the risk of upper gastrointestinal
bleeding, particularly if given in conjunction with non​steroidal anti-​
inflammatory drugs (NSAIDs).
Newer antidepressants
Main drugs
These can be classified as (a) selective serotonin-​noradrenaline re-
uptake inhibitors—​duloxetine and venlafaxine; (b) monoamine re-
ceptor antagonists—​mirtazapine and trazodone.
Venlafaxine is a potent blocker of 5-​HT reuptake and at higher
doses blocks the reuptake of noradrenaline as well. Duloxetine has
a similar action. Both trazodone and mirtazapine are 5-​HT2 re-
ceptor antagonists and block α1-​adrenoceptors in addition, which
gives them a sedating profile. Mirtazapine also blocks inhibitory
presynaptic α2-​adrenoceptors, resulting in an increased release of
noradrenaline.
Indications and use
These antidepressants can be used to treat patients in whom SSRIs
are poorly tolerated or found to be ineffective. With the exception of
venlafaxine, these drugs lack significant cardiotoxicity and are rela-
tively safe in overdose.
Adverse effects
The main adverse effects of the other, newer antidepressants are
shown in Table 26.4.1.2. The major distinction between compounds
is whether they are sedating.
Drug interactions
Duloxetine and venlafaxine, like SSRIs, potentiate 5-​HT function
and therefore can cause serious 5-​HT neurotoxicity. Trazodone
and mirtazapine may increase the sedative effects of other centrally
acting drugs.
Tricyclic antidepressants
Tricyclic antidepressants (TCAs) inhibit the neuronal uptake of nor-
adrenaline and 5-​HT. They have numerous other pharmacological
properties, which contribute to their adverse effects rather than their
therapeutic activity. However, some of these adverse effects (e.g. sed-
ation) can prove beneficial in certain circumstances.
Main drugs
These
are
amitriptyline,
clomipramine,
lofepramine,
and
nortriptyline.
Indications and use
Tricyclic antidepressants are now little used for the treatment of de-
pression, but are still widely prescribed at relatively low doses as ad-
juncts for the management of pain and insomnia.
Adverse effects
These are listed in Table 26.4.1.3.
Drug interactions
The ability of TCAs to block noradrenaline reuptake can lead to
hypertension with systemically administered noradrenaline and
adrenaline (epinephrine). Tricyclic antidepressants should not
be used in conjunction with antiarrhythmic drugs, particularly
amiodarone. Numerous other drugs including sodium valproate,
calcium channel blockers, and SSRIs can increase the plasma levels
of tricyclic antidepressants.
Mood stabilizing drugs
Lithium
Lithium salts have inhibitory effects on receptor-​transduction
systems, particularly second messengers such as cAMP and
phosphoinositol.
The main uses of lithium are:
•	 prophylaxis of recurrent mood disorders, especially manic de-
pressive illness
•	 acute treatment of mania
•	 augmentation of antidepressant medication in patients with re-
sistant depression
Lithium remains a leading pharmacological treatment for the main-
tenance phase of bipolar disorder. However, because of its potential
toxicity and limited tolerability, anticonvulsant treatments and atyp-
ical antipsychotic drugs are increasingly used for this purpose.
The excretion of lithium from the body is critically dependent on
the kidneys. Since there is little margin between therapeutic serum
levels of lithium (0.5–​0.8 mmol/​litre) and those causing toxicity
(>1.2 mmol/​litre) clinical and laboratory assessment of renal func-
tion should be done before starting treatment. Renal function tests
Table 26.4.1.3  Adverse effects of tricyclic antidepressants
Pharmacological action
Adverse effects
Muscarinic receptor blockade
(anticholinergic)
Dry mouth, tachycardia, blurred
vision, glaucoma, constipation,
urinary retention, sexual dysfunction,
cognitive impairment
α1-​Adrenoceptor blockade
Drowsiness, postural hypotension,
sexual dysfunction, cognitive
impairment
Histamine H1 receptor blockade
Drowsiness, weight gain
Membrane stabilizing properties
Cardiac conduction defects, cardiac
arrhythmias, epileptic seizures,
overdose toxicity
Other
Rash, oedema, leucopenia, elevated
liver enzymes
section 26  Psychiatric and drug-related disorders
6468
should include urinalysis and measurement of plasma creatinine
and electrolyte levels: care should be taken if there is any suggestion
of impaired renal function (reduced estimated GFR (eGFR)).
In the absence of clinical indications, it is usually sufficient to
check lithium levels every three months and to repeat renal func-
tion tests every six months. Lithium can also cause hypothyroidism,
so thyroid function tests should be done prior to treatment and at
six-​monthly intervals thereafter. If necessary, thyroxine replacement
therapy can be added. Sudden withdrawal of lithium in patients
with bipolar disorder can cause an acute rebound mania and should
therefore be avoided if possible.
Adverse effects
The side effects of lithium are shown in Table 26.4.1.4.
The most important are a result of the effect on the kidneys. Some
degree of thirst and polyuria is common, and a few patients de-
velop nephrogenic diabetes insipidus, probably caused by lithium
blocking the effect of antidiuretic hormone on the renal tubule.
Most patients taking lithium have a demonstrable impairment of
tubular concentrating ability, although this is rarely of clinical sig-
nificance. Glomerular function is less affected by lithium, but glom-
erular damage and interstitial fibrosis have been reported following
lithium toxicity. While long-​term lithium treatment, even at thera-
peutic plasma levels, can cause long-​term renal impairment and
renal failure, this risk can be minimized by maintaining the serum
concentration within the therapeutic range. An increasing level of
creatinine/​decreasing level of eGFR (a fall of more than 4 ml/​min
per year, or to a value <30 ml/​min) should prompt review by a renal
physician.
Drug interactions
The narrow therapeutic index of lithium means that drug inter-
actions that raise serum lithium levels can have serious clinical
consequences. Important interactions can occur with diuretics,
NSAIDs, ACE inhibitors, and angiotensin II receptor antagonists,
all of which may increase lithium levels. Lithium levels may be in-
creased by metronidazole and lowered by theophylline and antacids.
While the effects of lithium on cardiac conduction are usually con-
sidered benign, it may potentiate the effects of cardiac glycosides on
conduction.
Toxicity
Acute lithium toxicity usually appears at a serum level above
1.2 mmol/​litre. Early signs are coarse tremor, drowsiness, and dys-
arthria. Higher plasma concentrations (>2.0 mmol/​litre) can lead to
seizures, coma, and death. Since lithium toxicity is potentially fatal,
any suspicion of intoxication should lead to the immediate with-
drawal of lithium treatment and close monitoring of serum lithium
and plasma electrolyte and creatinine concentrations. Severely ill
patients with high serum lithium levels may require dialysis.
Sodium valproate
Valproate is a simple branched-​chain fatty acid with a mode of ac-
tion that is unclear, although there is some evidence that it can slow
the breakdown of the inhibitory neurotransmitter γ-​aminobutyric
acid (GABA). This action could account for its anticonvulsant
properties, but whether it also underlies the psychotropic effects
is unclear.
Indications and use
Valproate is effective in the management of acute mania and in
the longer-​term prophylaxis of bipolar disorder. Valproate can be
started at a dose of 200–​400 mg daily, which may be increased once
or twice weekly to between 1 and 2 g daily. Plasma levels of val-
proate do not correlate well with either its anticonvulsant or mood
stabilizing effects, but it has been suggested that efficacy in the treat-
ment of mood disorders is usually apparent when plasma levels are
above 50 µg/​ml.
Side effects
Common side effects of valproate include gastrointestinal disturb-
ances, tremor, sedation, weight gain, and transient hair loss. Serious
side effects are rare, but fatal hepatic toxicity and acute pancreatitis
can occur. Valproate may also cause thrombocytopenia and inhibit
platelet aggregation, and increases in plasma ammonia can occur.
Drug interactions
Valproate potentiates the effects of central sedatives. It can in-
crease the side effects of other anticonvulsants (without necessarily
improving anticonvulsant control). It may increase plasma levels of
phenytoin and TCAs.
Other drugs
Although not licensed for this indication in the United Kingdom,
the anticonvulsant drug lamotrigine is increasingly used to
treat depression in patients with bipolar disorder. Atypical anti-
psychotic drugs such as quetiapine are also being used to treat bi-
polar disorder.
Antipsychotic drugs
Antipsychotic drugs, also known as major tranquillizers or neuro-
leptics, are a group of agents of varied structure used to treat
schizophrenia and other psychoses. All antipsychotic agents have
in common the ability to block dopamine receptors in the cen-
tral nervous system, and it is likely that their antipsychotic effect
is caused by blockade of dopamine D2 receptors in mesolimbic
Table 26.4.1.4  Adverse effects of lithium
Central nervous system
Drowsiness, lethargy, headache, memory
impairment, fine tremor
Cardiovascular system
Conduction defects (rare)
Gastrointestinal system
Nausea, vomiting, diarrhoea
Genitourinary system
Polydipsia, polyuria, nephrogenic diabetes
insipidus
Endocrine system
Hypothyroidism (T4 ↓ TSH ↑), hyperglycaemia,
hyperparathyroidism
Other
Leucocytosis, skin rash, weight gain
Signs of toxicity (plasma
level: >1.2 mmol/​litre)
Nausea, vomiting, coarse tremor, drowsiness,
dysarthria, seizures, coma, renal failure,
cardiovascular collapse
T4, thyroxine; TSH, thyroid stimulating hormone.
26.4.1  Psychopharmacology in medical practice
6469
regions of the brain. Blockade of D2 receptors in striatum explains
the common occurrence of various kinds of extrapyramidal move-
ment disorders.
The newer so-​called ‘atypical’ antipsychotic drugs have a varied
pharmacology, but are less likely to produce extrapyramidal side
effects at therapeutic doses than conventional agents such as halo-
peridol. Some atypical agents such as amisulpride, are highly selective
dopamine D2 receptor antagonists with selectivity for mesolimbic
dopamine receptors. Others (e.g. risperidone, olanzapine, and
quetiapine) have high affinities for the 5-​HT2 receptor that exceed
their affinities for the D2 receptor.
Main drugs
These are:  (a) the conventional (typical) antipsychotic drugs—​
chlorpromazine, haloperidol, flupentixol, fluphenazine; (b)  atyp-
ical antipsychotic drugs—​amisulpride, aripiprazole, clozapine,
olanzapine, quetiapine, and risperidone.
Indications and use
The main use of antipsychotic drugs is to treat schizophrenia. They
are also used to treat mania and are sometimes given to depressed
patients who have psychotic symptoms or who are particularly agi-
tated. Some atypical antipsychotic drugs (for example, quetiapine
and olanzapine) are helpful in the maintenance treatment of bipolar
disorder and quetiapine has useful effects in the acute treatment of
bipolar depression.
Antipsychotic drugs are also used in the management of
disturbed behaviour arising from other medical causes (e.g.
confusional states), but their use as non​specific tranquillizing
agents should be short-​term only because of their potentially ser-
ious side effects. Some groups of demented patients (particularly
those with Lewy body type dementia) can suffer severe extra-
pyramidal effects from comparatively low doses of antipsychotic
drugs. Patients with dementia also appear to be at increased risk
of adverse cardiovascular events, particularly stroke, during anti-
psychotic drug treatment. Antipsychotic drugs increase the risk of
thromboembolic disease.
Clozapine can be effective in up to 30% of patients with schizo-
phrenia whose symptoms have not responded to other antipsychotic
drugs (both typical and atypical). Notably it is effective in the treat-
ment of both positive and negative symptoms of schizophrenia; the
latter often responding poorly to other antipsychotic drugs.
Adverse effects
Abnormal movements
Through their blockade of brain dopamine receptors, typical anti-
psychotic drugs commonly produce a variety of extrapyramidal
movement disorders that can mimic signs of basal ganglia disease,
for example, acute dystonia and parkinsonism. The treatment of
these movement disorders is by a reduction in dosage of the anti-
psychotic drug or by the introduction of anticholinergic medica-
tion such as benztropine. After a period of treatment, tardive (late
onset) dyskinesia may develop. This consists of involuntary repeti-
tive movements, usually involving the tongue and lips, though other
parts of the body may be involved. Unfortunately, these movements
are hard to treat and anticholinergic medication may make them
worse. If possible, the antipsychotic drug should be stopped; this de-
cision is often difficult because of the risk of relapse of the psychiatric
disorder it is being used to treat. Atypical antipsychotic drugs are
less likely to cause movement disorders including tardive dyskinesia.
Weight gain
Many antipsychotic drugs can cause weight gain; the risk is greatest
with atypical agents, particularly clozapine, olanzapine, and quetiapine.
These drugs are also associated with a greater risk of type 2 diabetes
than conventional agents, as well as disturbances in lipid profile.
Patients taking atypical antipsychotics should therefore be monitored
for weight gain and disturbances in glucose and lipid metabolism.
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a rare but potentially very ser-
ious reaction to antipsychotic drugs. It is characterized by fever,
muscular rigidity, altered consciousness, tachycardia, and labile
blood pressure. Abnormal investigations include leucocytosis and
markedly raised creatinine phosphokinase. Management is by im-
mediate withdrawal of the antipsychotic drug. The drugs bromo-
criptine and dantrolene may be helpful. If there are cardiovascular,
respiratory, and renal complications, ICU support may be required.
The most common adverse effects of atypical antipsychotic drugs
are shown in Table 26.4.1.5.
Drug interactions
Antipsychotic drugs potentiate the effects of other central sedatives.
They may delay the hepatic metabolism of TCAs and antiepileptic
drugs, leading to increased plasma levels of these agents. Clozapine
Table 26.4.1.5  Adverse effects of atypical antipsychotic drugs
Drug
EPS
Prolactin
Weight gain
Adverse effects
Amisulpiride
+
↑
+
Insomnia, agitation, nausea, constipation, QT prolongation (rare)
Clozapine
0
0
+++
Agranulocytosis—​regular white cell monitoring mandatory, myocarditis and
myopathy (rare), fatigue, drowsiness, hypersalivation, sweating, tachycardia,
postural hypotension, nausea, constipation, ileus, urinary retention, diabetes
Olanzapine
+/​0
0
+++
Somnolence, dizziness, oedema, hypotension, dry mouth, constipation,
diabetes
Quetiapine
0
0
++
Somnolence, dizziness, postural hypotension, dry mouth, abnormal liver
function tests, QT prolongation, diabetes
Risperidone
+
↑
+
Insomnia, agitation, anxiety, headache, impaired concentration, nausea,
abdominal pain
0, not present; +, sometimes; ++, often; +++, can be excessive; EPS, extrapyramidal symptoms.

26.4.2 Psychological treatments 6470 Michael Sharp
26.4.2 Psychological treatments 6470 Michael Sharpe and Simon Wessely
section 26  Psychiatric and drug-related disorders
6470
should not be given with any agent likely to potentiate its depressant
effect on the white cell count such as carbamazepine, co-​trimoxazole,
and penicillamine. SSRIs slow the hepatic metabolism and increase
blood levels of several antipsychotic drugs, including haloperidol,
risperidone, and clozapine.
Antianxiety agents
Benzodiazepines
Benzodiazepines enhance the action of the neurotransmitter γ-​
aminobutyric acid (GABA) in the central nervous system binding
to a specific benzodiazepine receptor located in a complex with a
GABA receptor and a chloride ion channel. The pharmacological
effects of benzodiazepines are attributed to the facilitation of GABA
neurotransmission.
Main drugs
These are diazepam, lorazepam, and temazepam.
Indications and use
The prescription of benzodiazepines is decreasing following con-
cern about their liability to produce dependence with long-​term
use. Alternative therapies are available for chronic anxiety related
disorders, and it is recommended that benzodiazepine treatment of
anxiety and insomnia should be limited to two weeks only. The main
indication for the use of benzodiazepines is for patients with acute
stress reaction and adjustment disorders in which anxiety and in-
somnia are reducing their ability to cope. Patients should be advised
that the drug treatment will only be of short duration.
All benzodiazepines have hypnotic and anxiolytic properties; the
main difference between them of clinical importance is their length
of action. Derivatives with short half-​lives, such as temazepam, are
suitable hypnotics because of their relative lack of a hangover effect.
Other benzodiazepines (e.g. diazepam) have long half-​lives and are
metabolized to active compounds. They either may be used for the
treatment of anxiety, in the form of regular dosing, or in the now
preferred ‘as required’ basis with an agreed maximum daily dose.
Side effects and interactions
Benzodiazepines have a low acute toxicity. Their adverse effects are
extensions of their clinical effects and include drowsiness, psycho-
motor impairment, dizziness, ataxia, and paradoxical aggression
(rare). Benzodiazepines potentiate the effects of other centrally
acting sedatives, particularly alcohol. The effects of benzodiazepines
are potentiated by cimetidine.
Patients who have taken clinical doses of a benzodiazepine for
more than a few weeks may show a withdrawal syndrome when the
medication is stopped. This syndrome resembles an anxiety state,
but perceptual disturbances and dysphoria may also occur. It is
thus apparent that benzodiazepines can cause physical dependence,
and patients frequently find it difficult to stop their medication.
A gradual reduction in dose is usually best.
Zopiclone, zolpidem, zaleplon (the Z drugs)
The ‘Z drugs’ are non​benzodiazepine agents with short half-​lives
that also increase GABA function by binding to the benzodiazepine
­receptor and are licensed as hypnotics. The treatment of insomnia
with either benzodiazepines or the Z drugs should be short-​term to
avoid dependence.
Other drugs
SSRIs are effective in the management of a range of anxiety dis-
orders, including generalized anxiety, and phobic states. SSRIs are
also effective in the treatment of obsessive–​compulsive disorder.
FURTHER READING
Baldwin DS, et al. (2014). Evidence-​based guidelines for the pharma-
cological treatment of anxiety disorders, post-​traumatic stress dis-
order and obsessive compulsive disorder:  a revision of the 2005
guidelines from the British Association of Psychopharmacology. J
Psychopharmacol, 28, 403–​39.
Cleare A, et al. (2015). Evidence based guidelines for treating depres-
sive disorders with antidepressants: a revision of the 2008 British
Association for Psychopharmacology guidelines. J Psychopharmacol,
29, 459–​525.
Goodwin GM, et al. (2016). Evidence-​based guidelines for treating bipolar
disorder:  revised third edition—​recommendations from the British
Association of Psychopharmacology. J Psychopharmacol, 30, 495–​553.
Harrison P, Cowen P, Burns T, Fazel M (2018). Drugs and other physical
treatments. In: Harrison P, et al. (eds), The shorter Oxford textbook of psy-
chiatry, OUP, 7th edition, pp. 709–​75. Oxford University Press, Oxford.
Stahl SM (2013). Essential psychopharmacology, 4th edition. Cambridge
University Press, Cambridge.
Taylor D, Barnes TRE, Young AH (2018). The Maudsley prescribing
guidelines, 13th edition. Wiley Blackwell, Chichester.
26.4.2  Psychological treatments
Michael Sharpe and Simon Wessely
ESSENTIALS
Psychological treatments, sometimes called psychotherapies or talking
treatments, refer to the use of psychological, as opposed to pharma-
cological or surgical methods, to treat an illness or improve a person’s
well-​being. They may be regarded as general or specific in type.
General psychological treatments, such as listening to the patient
and providing reassurance, are a core aspect of general medical prac-
tice as all medical interactions will have a psychological impact on
the patient, whether for good or ill. Specific psychological therapies,
which are usually given by trained therapists, are important treatments
for psychiatric illnesses such as depression and anxiety. Consequently,
it is important that physicians both know how to make their consult-
ations generally psychotherapeutic and about specific psychological
treatments, so that they can refer patients appropriately for these.
What is psychological treatment?
Psychological or talking treatments are also referred to as
psychotherapies. They target the patient’s psychological processes
26.4.2  Psychological treatments
6471
with the aim of improving their well-​being. They are delivered mainly
by listening and talking, and increasingly also via digital media.
They aim to help patients to change their understanding, emotional
response to and behaviour towards their illness or situation. General
psychological treatments, such as listening to the patient and pro-
viding reassurance, are a core aspect of general medical practice as
all medical interactions will have a psychological impact on the pa-
tient, whether for good or ill. In this sense, all doctors, whether they
know it or not, are in the business of delivering psychotherapy.
Specific psychological treatments are more intensive and tailored
interventions designed to treat specific problems or illnesses. There
is a wide variety of ‘psychotherapies’ including counselling, psycho-
dynamic, and various forms of cognitive behavioural therapy (CBT).
Specific psychological treatment is an important and evidence-​
based method of treating many psychiatric illnesses and other psy-
chological problems, including those that may complicate general
medical care.
The psychotherapeutic medical
consultation
The medical consultation is a psychotherapeutic opportunity. This
was perhaps better understood when physicians had less to offer,
and indeed to do, in terms of carrying out biological investigations
and treatments. There was then a greater need, and opportunity, to
seek benefit from simply listening to and talking with the patient.
However, despite the power of modern medicine’s pharmacological
and surgical treatments, psychotherapeutic aspects of the consult-
ation remain important to the effective practice of medicine. This is
especially the case when there is diagnostic uncertainty, a need for
the patient to adhere to a treatment regimen, or when the patient has
coexisting psychiatric illness or distress.
Psychotherapeutic consultations (doing good)
Key requirements for a positively psychotherapeutic consultation
are shown in Box 26.4.2.1.
Although many medical encounters are suboptimal in delivering
these ingredients, they can be easily improved by simply fol-
lowing the recommendations summarized in Table 26.4.2.1 and
described next.
Preparing well
If possible read the patient’s notes in advance and decide how you
can best use the consultation therapeutically, and not simply to
gather data (much of which may already be recorded). Pay attention
to the physical arrangements for the consultation. The days when
patients were told that they have cancer on an open ward round
may have gone, but many consultations still offer scant privacy
and provide little real opportunity for the patient to ask ques-
tions. Preparation for the right place and time helps to make best
use of the consultation. It is important that the need for time and
privacy is recognized and if necessary insisted on by the physician
despite institutional pressures. Time with the patient is an essen-
tial therapeutic tool that, like a drug, will only work if given in an
appropriate dose.
Listening well
Taking an interest in the patient’s symptoms (even those that are
not of diagnostic value) and their fears about these (even if they
appear illogical) is important for two reasons. First, it helps the pa-
tient to feel that their concerns have been heard, resulting in better
adherence to the physician’s advice. Second, effective reassurance
requires learning what it is that the patient fears. Time spent on
such matters is therefore a critical means for helping the patient to
feel better.
Explaining well
A  clear explanation of the physician’s understanding of the
patient’s problem is required. While it may sound obvious, this
requires a clear statement and explanation of the diagnosis when-
ever possible. All too often patients complain that doctors have
told them what they did not have, but not what they did have.
This most often happens when the patient’s complaints are not
adequately explained by identifiable disease (medically unex-
plained) (see Chapter 26.3.3).
Making a shared plan
Even when a clear diagnosis or specific treatment cannot be given,
a positive plan of action usually can. There is evidence that such a
positive approach has a beneficial effect. The provision of hope, the
agreement on a practical plan, and an expectation of improvement
in at least some aspects of the illness, have long been key ingredi-
ents of an effective doctor–​patient relationship. Although the hope
offered should not be false (e.g. if the patient has a terminal condi-
tion, it is clearly unhelpful to pretend otherwise), the message given
to the patient can still be a positive one (e.g. the symptoms will be
managed and the doctor will provide ongoing help). A written sum-
mary of the plan, perhaps as a copy of the letter to another doctor, is
usually helpful.
Box 26.4.2.1  Psychotherapeutic imperatives for the medical
consultation
•	 Establish a good, confiding, and collaborative relationship with the
patient.
•	 Convince the patient that whatever the nature of their problem, you
can be trusted to help with it.
•	 Offer an acceptable and convincing explanation for what is wrong.
•	 Provide a positive and credible plan of action for addressing the
problem.
Table 26.4.2.1  Tasks for the physician in the medical consultation
Prepare
Ensure adequate time and privacy for the consultation,
and that you have the information you need.
Listen
Listen to the patient’s concerns about symptoms and
accept these as problems in their own right and not only
as pointers to disease.
Explain
Explain what you understand to be wrong, including a
diagnosis. Reassure about unfounded worries and provide
appropriate optimism.
Plan
Agree a plan with the patient with actions for both them
and for you. Ensure that they both understand and feel
understood. Summarize the plan in writing.
section 26  Psychiatric and drug-related disorders
6472
Psychological iatrogenesis (doing harm)
Like all treatments, the consultation has the potential to do psycho-
logical harm as well as good. Iatrogenesis can result not only from
prescribing the wrong drug or doing the wrong operation, but also
from what doctors say to their patients.
Poor listening
Appearing not to hear and accept the patient’s account of their
suffering can cause harm. For example, by telling a patient with
medically unexplained symptoms, ‘there is nothing wrong with
you’. This may not only damage your relationship with the patient,
but may also send him or her into the arms of less scrupulous
practitioners.
Unhelpful explanations
Ill-​considered or unhelpful explanations for the illness; for example,
telling the person who is depressed that it’s ‘probably a virus’, or a
person with back pain that they have a ‘weak ligament’ send false
messages about why they are unwell. It will also influence what
treatment they should seek and may worsen the clinical outcome by
influencing their behaviour.
Unrealistic prognostication
Both excessively optimistic predictions; for example, telling a pa-
tient who has not yet been adequately assessed ‘I’m sure it’s nothing
serious’ and excessively pessimistic predictions (e.g. telling a person
with possible multiple sclerosis ‘it’s probably best if you just come to
terms with the idea of a wheelchair now’) may be harmful. Both risk
loss of credibility of the physician if the predictions are not fulfilled.
They may also lead to the patient acting on inaccurate information
and to unnecessary distress.
Harmful advice
Poorly thought out or ill-​informed advice can do more harm than
might be imagined. A  compelling demonstration of this type of
problem was found in a study of schoolchildren whose parents
were told (sometimes incorrectly) that their children had abnormal
hearts and should avoid exertion: at follow up many years later, the
children with normal hearts whose parents were warned incorrectly
about activity were restricting their activity as much as those with
heart disease.
Specific psychological treatments
Specific psychological treatments may be broadly divided into the
following types: (a) simple brief therapies, usually given over one
to less than 10 sessions by a person with modest training; (b) more
complex but usually brief psychotherapies, such as CBT, which may
be given over 6 to as many as 20 sessions and require a highly trained
therapist; (c) longer-​term treatments such as psychodynamic psy-
chotherapy, which may be given over months or years and require a
very high level of therapist skill. See Table 26.4.2.2.
Specific psychotherapies are an important tool in the treat-
ment of psychiatric illnesses. They also have a potentially im-
portant role in the management of medical illness by providing
evidence-​based treatments for symptoms such as fatigue and pain,
reducing emotional distress, and improving adherence to medical
treatments. There is a strong argument that many patients would
benefit from better integration of these psychotherapies into their
medical care.
Simple brief therapies
Brief counselling
Counselling, usually given by trained councillors, can help patients
to express distress and talk through problems such as a diagnosis of
cancer. However, basic counselling should also be regarded as a gen-
eric skill that all doctors and nurses are able to provide.
Motivational interviewing
This is a simple technique to encourage behaviour change. It aims
to help the patient clarify what they want to achieve, then to con-
sider the advantages and disadvantages of specific behaviours as
ways of achieving it. It can be delivered during a single extended
consultation. Originally developed to help people reduce problem
drinking, it has wider application to many situations where behav-
iour change is required, such as improving adherence to medical
treatment.
Problem solving therapy
A brief (typically six to eight sessions) simple psychological treat-
ment that aims to help patients feel more in control of the practical
problems they face. It teaches them to define their problems clearly,
to tackle them one at a time, and to work out clear strategies to over-
come them. It is effective for treating depression.
Behavioural activation
A simple therapy that helps patients to become generally more ac-
tive and specifically to overcome avoidance of important activities.
When given by a trained therapist, it is effective in the treatment of
depression.
Complex but usually brief therapies
Cognitive behaviour therapy (CBT)
CBT is a complex therapy usually given over 6–​20 sessions. It re-
quires a skilled therapist. The cognitive part refers to helping the
patient to re-​evaluate and optimize their thinking, for example,
countering excessive pessimism about their medical condition.
Table 26.4.2.2  Commonly used psychotherapies
Simple brief therapies
•	 Brief counselling
•	 Motivational interviewing
•	 Problem solving
•	 Behavioural activation
Complex but usually brief
therapies
•	 Cognitive behaviour therapy
•	 Acceptance and commitment therapy
•	 Mindfulness training
•	 Interpersonal therapy
Longer-​term treatments
•	 Long-​term counselling
•	 Psychoanalysis
•	 Long-​term forms of CBT
26.4.2  Psychological treatments
6473
The behavioural part involves helping them to cope more ef-
fectively by reducing unhelpful behaviours such as excessive
checking of symptoms or avoidance of activities. It is effective
in the treatment of patients with depression, anxiety, and panic
disorders and in the treatment of medically unexplained or func-
tional symptoms.
Mindfulness training
Mindfulness is not really a therapy, but rather training in a skill. It
aims to help the patient develop ‘mindfulness’; the psychological pro-
cess of focusing attention on only those internal and external experi-
ences occurring in the present moment and accepting rather than
judging these. It requires prolonged diligent practice. It is currently
being widely advocated for several problems. The strongest evidence
of its efficacy is in the prevention of relapse in patients with depres-
sion. The evidence to support its many other potential applications,
such as the treatment of symptoms and occupational stress, is weaker.
Acceptance and commitment therapy
This is a form of CBT, which also includes elements of mindfulness.
It has two main components: the first is helping the patient to ac-
cept their thoughts, emotions, and symptoms and not to challenge
or struggle against them. The second is to encourage the patient to
commit to changing their behaviour, however they feel. An example
might be accepting pain as incurable; to accept rather than resent it
and to commit to re-​establishing previously valued activities, even if
this increases pain. The evidence of efficacy is strongest in the man-
agement of chronic pain.
Interpersonal therapy
This short-​term therapy focuses on helping the patient to under-
stand their personal relationships and how these relate to the prob-
lems they have. They are then helped to make necessary changes.
An example may be a patient gaining understanding of how they
allow themselves to become excessively passive when ill, in part as
a response to an oversolicitous partner. The evidence of efficacy is
strongest for depression.
Complex longer-​term therapies
Long-​term counselling
This is supportive listening for someone with a long-​term problem.
Sessions may be spread over a long period, perhaps monthly for a
year or more. It may be of value in prolonged adjustment disorders
such as to a severe illness. It is not an effective treatment for more
severe problems such as major depressive disorder.
Psychodynamic therapy
For people with problems not amenable to a brief therapy, such as
those with major personality difficulties, there is a case for longer-​
term psychological therapy. One well-​established type of long-​
term therapy is psychodynamic psychotherapy. This is a modern
derivative of classical psychoanalysis and typically focused on the
relationship of current difficulties to experiences in childhood and
relationships with parents. It may last for many months or even
years. However, the availability of such therapy is limited and the
evidence for its effectiveness is modest.
Long-​term forms of CBT
Not all forms of CBT are brief. Long-​term CBT is used to treat
more severe problems such as personality disorder. For example,
there is evidence that a form of CBT called dialectic behaviour
therapy helps to improve the functioning of people with a form
of personality disorder called borderline personality disorder.
This therapy uses the relationship between patient and therapist
to produce therapeutic change and requires a high level of skill to
deliver.
Making a referral for a specific
psychological treatment
When considering a referral of a patient for psychological treatment,
the first requirement is to find out what services are available and
what types of referrals are accepted by these services. The second
requirement is to make sure that the patient understands why they
have been referred. The third requirement is to explain the referral to
the patient in a way that makes it likely that they will attend, at least
for an initial assessment.
Identifying psychological treatment services
Psychological treatment services would ideally be located in or-
ganizational and geographical proximity to where medical con-
sultations takes place; a psychotherapist in every clinic. In reality
they rarely are. It is therefore desirable for the physician to famil-
iarize themselves with what is provided by other organizations,
how long the patient will have to wait, and what kind of refer-
rals are likely to be accepted, before the need to make a referral
arises.
Making the referral
It is often helpful to discuss the type of problem being referred with
the service to ensure it will be accepted, before telling the patient.
For example, the patient’s psychological problems may appear ob-
viously in need of treatment to the physician, but regarded as an
untreatable personality disorder by a service providing only brief
therapy. If medical investigation or treatment is ongoing, it will help
if any uncertainties in diagnosis or prognosis are made explicit in
the referral letter, together with the physician’s plan for follow up of
the patient.
Explaining the referral to the patient
While telling the patient that they are being referred sounds simple,
it is most likely to be successful if care is taken when doing it. First,
and perhaps most important, is the need to make it clear that you are
not implying that the illness is ‘imaginary’ or ‘all in the mind’. Rather,
it can be explained that, as with almost all sick people, there is an
understandable psychological aspect to their problems that deserves
attention. Second, it helps to convey a positive attitude towards psy-
chotherapy as a sensible treatment approach with a good chance of
helping. It is even better if you can explain to the patient what they
can expect during the therapy. Finally, it is important, if appropriate,
to make sure the patient knows that, if required, you will see them
after the psychological treatment has finished, thereby making it
section 26  Psychiatric and drug-related disorders
6474
clear that you regard the referral as a useful addition to care and not
simply as a way of ‘getting rid of the patient’.
FURTHER READING
Burns T (2015). Psychotherapy: a very short introduction (very short
introductions). Oxford University Press, Oxford.
Farias M, Wikholm C, Delmonte R (2016). What is mindfulness-​based
therapy good for? Lancet Psychiatry, 3, 1012–​3.
Frank JD (1967). Persuasion and healing: a comparative study of psycho-
therapy. The Johns Hopkins University Press, Baltimore, MD.
Miller WR, Rollnick S (2013). Motivational interviewing: helping people
change, 3rd edition. The Guilford Press, New York, NY.
Thomas KB (1987). General practice consultations: is there any point
in being positive? BMJ, 294, 1200–​2.

26.5 Specific psychiatric disorders 6475 26.5.1 De
26.5 Specific psychiatric disorders 6475 26.5.1 Delirium 6475 Bart Sheehan
CONTENTS
26.5.1	 Delirium   6475
Bart Sheehan
26.5.2	 Dementia   6478
Bart Sheehan
26.5.3	 Organic psychoses   6482
Curtis McKnight and Jason Caplan
26.5.4	 Alcohol misuse   6486
Jonathan Wood
26.5.5	 Substance misuse   6490
Stephen Potts
26.5.6	 Depressive disorder   6493
Joseph Cerimele and Lydia Chwastiak
26.5.7	 Bipolar disorder   6498
Kate E.A. Saunders and John Geddes
26.5.8	 Anxiety disorders   6501
Ted Liao and Steve Epstein
26.5.9	 Acute stress disorder, adjustment disorders, and
post-​traumatic stress disorder   6506
Jonathan I. Bisson
26.5.10	 Eating disorders   6509
Christopher G. Fairburn
26.5.11	 Schizophrenia   6513
Stephen M. Lawrie
26.5.12	 Somatic symptom and related disorders   6517
Michael Sharpe
26.5.13	 Personality disorders   6520
Iain Jordan
26.5.1  Delirium
Bart Sheehan
ESSENTIALS
Delirium is one of the most common psychiatric problems encoun-
tered in elderly medical inpatients. It involves a fluctuating cognitive
impairment with reduced alertness and often with poorly formed
delusions and/​or visual hallucinations. The main differential diag-
nosis is from dementia, although delirium is more likely to develop in
patients with existing dementia.
Almost any medical condition that affects brain function may
cause delirium. Infection is the most common cause, and it is im-
portant to consider prescribed drugs as a cause and to remember
drug and alcohol withdrawal. Imperatives in management are first
to keep the patient safe from harm (they may wander or put them-
selves in danger), and second to find and correct the cause. Urgent
medical investigation and treatment is required as long periods of
delirium put the patient at risk of harm, including permanent cogni-
tive impairment.
Introduction
Delirium is the main cause of acute decline in cognitive function
and may be thought of as ‘acute brain failure’. It is caused by either
a direct insult to the brain (such as prolonged status epilepticus or
a brain abscess) or the response of a vulnerable brain to a systemic
insult (e.g. a patient with Alzheimer’s disease who becomes acutely
confused when developing a urinary tract infection). The subjective
experience of an episode of delirium is sometimes later recalled;
even if lacking dramatic symptoms like hallucinations and delu-
sions, patients may report feeling puzzled, frightened, and unable to
comprehend sensory inputs.
Aetiology
Table 26.5.1.1 lists common causes of delirium. The profile of a high-​
risk patient is well-​established: older people with existing dementia,
sensory impairment, and a history of previous stroke, depression,
alcohol abuse, or delirium.
Precipitating factors may be directly and sufficiently causal; for
example, a new anticholinergic drug, status epilepticus, and se-
vere alcohol withdrawal. In many cases the precipitating factor
may seem insufficient to provoke a delirium, leading to suspicion
that a vulnerable brain (for example due to dementia or previous
stroke) combined with an abnormal neuro-​inflammatory or al-
tered neurotransmitter response to external insult has triggered
the syndrome.
26.5
Specific psychiatric disorders
SECTION 26  Psychiatric and drug-related disorders
6476
Animal and human experimental work increasingly support this
hypothesis; thus insults such as an anticholinergic drug, or using
high dose lipopolysaccharides to mimic the effects of sepsis, lead
to clinical syndromes resembling delirium in vulnerable animals.
In humans, stress responses to insults, including elevated circu-
lating glucocorticoids, or exaggerated blood and cerebrospinal fluid
(CSF) cytokine responses, are hypothesized to mediate the physio-
logical pathway leading to the clinical signs of delirium, which may
themselves be mediated by altered cholinergic and monoaminergic
neurotransmission. There may be multiple causes.
Epidemiology
Delirium is probably the psychiatric condition most frequently rec-
ognized in general hospitals, though cases occur in other settings. It
has been most studied in general hospitals, where prevalence figures
of 15–​25% are typically found on orthopaedic, geratology, and gen-
eral medical wards. The highest prevalence (up to 50%) is found in
postsurgical intensive care unit (ITU), and in palliative care wards.
The prevalence in nursing home settings is around 10–​15%. In the
community the prevalence is probably only 1–​2%.
Clinical features
Box 26.5.1.1 outlines the diagnostic features of delirium. The car-
dinal criteria are inattention and reduced awareness of the environ-
ment. Recent criteria emphasize disorientation to the environment
as evidence of reduced awareness, acute change compared to base-
line function, and the broadening of aetiologies to include sub-
stance misuse and toxins. Fluctuation, often worse at night, and
visual hallucinations, often of a frightening nature, are common.
The patient may exhibit a hyperactive form with agitation and dis-
turbed behaviour, or sometimes a hypoactive form with reduced
activity
Differential diagnosis
The main differential diagnosis is from dementia. Other differentials
to consider are brain lesions such as concussion and cerebral malig-
nancy (primary and secondary). Delusions and hallucinations occur
in acute functional psychoses (though less often visual in nature).
The overactivity of mania may suggest hyperactive delirium and the
inactivity of depression hypoactive delirium, a key difference being
the reduced consciousness level in delirium. Drug and alcohol in-
toxication can cause a similar picture to delirium, but their presence
is often obvious.
Clinical investigation
Delirium is often not recognized and as many as two-​thirds of
cases are missed. The diagnosis is more likely to be made if the
patient has the overactive rather than underactive form. Clinical
experience is often essential to recognize the signs in more subtle
presentations. Key to the diagnosis is the recognition of the core
clinical features, especially inattention and fluctuating conscious-
ness. These are emphasized in the published diagnostic criteria
such as ICD-​10 and DSM-​5. There are instruments available to
support the diagnosis such as the Confusion Assessment Method
(CAM) which focuses on acute onset and fluctuating course, and
inattention, supported by disorganized thinking and altered con-
sciousness. At the very least, a test of attention (e.g. counting back
from 20)  and of orientation (e.g. year/​season/​month/​date/​day)
should be attempted. Characteristically, scores on such tests will
vary over time.
Medical assessment should seek the causes, beginning with the
commonest causes of delirium such as infection or dehydration. An
electroencephalogram (EEG) is sometimes used: typically there will
be diffuse slowing and increased θ and δ-activity. This can help dif-
ferentiate delirium from dementia but is rarely of significant prac-
tical value. There may also be a need to assess for hearing or visual
impairment.
Table 26.5.1.1  Common causes of delirium
Examples
Predisposing factors
(established risk factors
from prospective
studies)
Older age
Dementia
Alcohol misuse
Stroke
Depression
Hearing impairment
Visual impairment
Multimorbidity
Functional impairment
Urinary catheter
Precipitating factors
(selected)
Polypharmacy
Specific medications
Infections
Renal impairment
Hypothermia
Dehydration
Trauma
Infection
Hypoxia
Hypoglycaemia
Alcohol and drug
withdrawal
Anticholinergics
Sedatives
Antiparkinsonism drugs
Urinary tract infection
Respiratory tract
infection
Delirium tremens
Box 26.5.1.1  Diagnostic features of delirium
•	 Reduced attention (i.e. reduced ability to direct, focus, sustain, and shift
attention) and awareness (reduced orientation to the environment)
•	 Acute onset of a change from the previous cognitive functioning
•	 Fluctuation during the course of a day, and often worse at night
•	 Other psychological disturbances (e.g. memory deficit, disorientation,
language, visuospatial ability, or perception), hallucinations (often
visual)
•	 Evidence from the history, physical examination, or laboratory findings
that the disturbance is a direct physiological consequence of another
medical condition, substance intoxication or withdrawal, or exposure
to a toxin
26.5.1  Delirium
6477
Management
Prevention
The high prevalence and incidence of delirium in general hospital
patients has led to considerable interest in its prevention. The onset
of delirium is particularly common in orthopaedic postoperative
patients and among unwell patients in intensive care units.
Pharmacological methods with potential to prevent delirium in-
clude antipsychotic agents, cholinesterase inhibitors, melatonin, or
anti-​inflammatory agents. To date, however, there is inadequate evi-
dence to recommend this strategy. Prevention should instead focus
on identifying higher risk patients and using complex interventions
to reduce their risk of delirium (see Table 26.5.1.2). These measures
are supported by evidence but require considerable multidiscip-
linary effort to implement. Some could be considered simply good
clinical care (regular checks for dehydration, constipation, early
mobilization, adequate pain relief). Others require a change in staff
behaviour, for example use of orientation devices, regular checks
on sensory aids like spectacles and hearing aids, pharmacist review
for medications, with anticholinergic effects and allowing family to
provide care outside visiting hours. Implementation of these meas-
ures can only happen if there is a ward-​ or hospital-​wide awareness
of delirium and a willingness to actively identify, prevent, and treat
the condition.
Reducing the duration of delirium
The treatment of delirium is an emergency. It is now clear that pro-
longed delirium is associated with worse outcomes. Patients may
come to harm from wandering or falls, and long periods of delirium
may exacerbate dementia. The principles of management are there-
fore to keep the patient from harm while seeking and treating the
underlying cause. In a significant minority of cases no specific cause
is found, and clinicians may be tempted to give antibiotics, especially
if infective causes are suspected (e.g. when inflammatory markers
are raised).
There is at best equivocal evidence for the effect of antipsychotics
and lorazepam in reducing the duration of delirium, and modest
evidence from at least one controlled trial that rivastigmine (a cho-
linesterase inhibitor) may lengthen duration of episodes. Routine
use of psychotropic medication to reduce delirium is therefore not
supported. Other proposed strategies, for example routine use of
anti-​inflammatory medication, are also unsupported by evidence.
Treating the symptoms of delirium
Given the lack of evidence that pharmacological treatment can re-
duce the length of an episode, its role is limited to treating distressing
symptoms.
Chlordiazepoxide (or equivalent doses of diazepam, or other
long-​acting benzodiazepine) is recommended for the treatment of
alcohol withdrawal and its major complication of delirium tremens.
For other causes, there is modest evidence to support the use of
olanzapine, risperidone, and haloperidol in treating aggression, dis-
tress, and psychotic symptoms in delirium. Local protocols usually
suggest dosing regimens; as most patients are frail, lower doses are
used than with younger patients with schizophrenia or mood dis-
orders (the usual indications).
These treatments should be withdrawn when symptoms re-
solve, as there is doubt about the risk/​benefit ratio after this time.
Benzodiazepines (usually short acting agents like lorazepam) are
sometimes used for behavioural control in distressed or aggressive
patients, but there is little evidence to support this.
Preventive and treatment interventions for delirium overlap con-
siderably. They include direct support of brain function including
reversing hypoxia and stopping deliriogenic drugs (see Box 26.5.1
and Table 26.5.2). Indirect support focuses on the environment of
care: using orientation clocks, involving family in care, promoting
sleep at night (e.g. using earplugs, side rooms), using single staff
members during shifts. The environment of care includes staff and
family carers, and responsible staff need to ensure that all carers
clearly understand the diagnosis and prognosis.
Outcome
Delirium is a strong independent predictor of prolonged hospital
stay, increased mortality, and of institutionalization. Delirium often
indicates an as-​yet undiagnosed dementia, while among patients
with delirium who do not currently have dementia, the risk of de-
mentia developing later is substantially increased. For those patients
with established dementia, incident delirium is shown to accelerate
the deteriorating course of dementia. For all of these outcomes, it ap-
pears that length of delirium is predictive of poor outcomes, making
shortening delirious episodes a legitimate management goal. It is
now also clear that delirium is by no means always transient. Meta-​
analyses show that nearly half of hospital cases are not yet resolved
at the point of discharge from hospital, while up to 20% remain deli-
rious six months after the index episode.
FURTHER READING
American Psychiatric Association: (2013). Diagnostic and statistical
manual of mental disorders, 5th edition. Arlington, VA.
Cole MG (2010). Persistent delirium in older hospital inpatients. Curr
Opin Psychiatry, 23, 250–​4.
Inouye SK, Westendorp RG, Saczynski JS (2014). Delirium in elderly
people. Lancet, 383, 911–​22.
Maclullich AM, et al. (2013). New horizons in the pathogenesis, assess-
ment and management of delirium. Age Ageing, 42, 667–​74.
Table 26.5.1.2  Preventive measures for delirium
Routine
Specific
Avoid use of urinary catheters
Use hearing aids and spectacles
Detect and treat constipation
Detect and treat pain
Early mobilization
Review nutritional and hydration status
Stratification for delirium risk
Secondary prevention—​screening (e.g. using CAM)
Orientation clocks
Pharmacy review for drugs that cause delirium
Sleep promotion
Proactive management of alcohol and drug withdrawal

26.5.10 Eating disorders 6509 Christopher G. Fairb
26.5.10 Eating disorders 6509 Christopher G. Fairburn
26.5.10  Eating disorders
6509
development of PTSD. The natural course of PTSD is to reduce
slowly over time; half of PTSD sufferers will no longer fulfil the full
criteria two years after onset, but a third will continue to do so after
six years.
FURTHER READING
Bisson JI (2014). Early responding to traumatic events. Br J Psychiatry,
204, 329–​30.
Bisson JI, et  al. (2013). Psychological therapies for chronic post-​
traumatic stress disorder (PTSD) in adults (review). Cochrane
Database Syst Rev, 12, CD003388.
Hoskins M, et al. (2015). Pharmacotherapy for post-​traumatic stress
disorder: systematic review and meta-​analysis. Br J Psychiatry, 206,
93–​100.
National Collaborating Centre for Mental Health (2005). Post-​
traumatic stress disorder: the management of PTSD in adults and
children in primary and secondary care. Gaskell and BPS, London
and Leicester.
National Institute for Health and Care Excellence (NICE) (2013). Evidence
update 49—​post-​traumatic stress disorder (PTSD). Manchester, NICE.
https://​arms.evidence.nhs.uk/​resources/​hub/​1031525/​attachment
26.5.10  Eating disorders
Christopher G. Fairburn
ESSENTIALS
The eating disorders are a group of conditions, central to which
is a disturbance of eating behaviour. The main diagnoses are an-
orexia nervosa and bulimia nervosa, in both of which there is an
extreme concern with weight and shape. In anorexia nervosa, per-
sistent dietary restriction leads to weight loss, which may be severe.
In bulimia nervosa, the dietary restriction is interrupted by re-
peated episodes of binge eating (typically followed by self-​induced
vomiting) and weight is usually unremarkable. Both disorders may be
accompanied by medical complications that present to physicians.
Anorexia nervosa has the potential to be life-​threatening because
of the consequences of starvation. Patients may require medical at-
tention for the correction of electrolyte disturbance and sometimes
admission to a medical unit for refeeding. The main treatment of
eating disorders is psychological. The prognosis of bulimia nervosa is
generally good but is less positive for anorexia nervosa.
Introduction
The eating disorders are conditions in which a persistent disturb-
ance of eating is the most prominent feature. There are two main
eating disorders, anorexia nervosa and bulimia nervosa, and a third
separate condition termed binge eating disorder. In addition, there
is a residual category (termed here ‘other eating disorders’ or OEDs)
reserved for eating disorders of clinical severity that do not meet
the diagnostic criteria for anorexia nervosa, bulimia nervosa, or
binge eating disorder. Box 26.5.10.1 lists their principal diagnostic
criteria.
Aetiology
The aetiology of the eating disorders is poorly understood. While
many risk factors have been identified (Box 26.5.10.2), it is not clear
how they operate and interact. The most prominent risk factors for
anorexia nervosa and bulimia nervosa are being young and female,
and living in a ‘Western’ culture in which slimness is prized and
dieting is common. The personality traits of perfectionism and low
self-​esteem appear to increase the risk of both disorders, as does a
family history of depression or an eating disorder. In common with
many psychiatric disorders, adverse childhood experiences are also
associated with an increase in risk. A family history of substance
misuse or obesity specifically increases the risk of binge eating, as
does an early menarche and a history of impulsivity.
Family-​genetic studies indicate an important genetic contribution
and there appears to be cross-​transmission between the eating dis-
orders, suggesting shared familial liability. Molecular genetic studies
have yielded inconsistent findings, probably in part because of small
sample sizes and problems defining the phenotype.
Box 26.5.10.1  Classification and diagnosis of the eating
disorders
Classification of eating disorders
•	 Anorexia nervosa
•	 Bulimia nervosa
•	 Binge eating disorder
•	 Other eating disorders (OEDs)1
Principal diagnostic criteria
Anorexia nervosa
1.  Overevaluation of shape and weight (i.e. judging self-​worth largely,
or exclusively, in terms of shape and weight)
2.  Active maintenance of an unduly low body weight (e.g. body mass
index <17.5)
Bulimia nervosa
1.  Overevaluation of shape and weight (i.e. judging self-​worth largely,
or exclusively, in terms of shape and weight)
2.  Recurrent binge eating (e.g. episodes of uncontrolled overeating at
least once a week)
3.  Extreme weight-​control behaviour (e.g. strict dietary restriction, fre-
quent self-​induced vomiting, or laxative misuse)
4.  Diagnostic criteria for anorexia nervosa are not met
Binge eating disorder
Recurrent binge eating in the absence of the extreme weight-​control
behaviour seen in bulimia nervosa
Other eating disorders
Eating disorders of clinical severity that do not meet the diagnostic
criteria for anorexia nervosa, bulimia nervosa, or binge eating disorder
1 The fifth edition of the American Psychiatric Association’s Diagnostic and Statistical
Manual of Mental Disorders refers to these states as ‘Other specified feeding or eating
disorder’.
SECTION 26  Psychiatric and drug-related disorders
6510
Once established, a variety of processes maintain an eating dis-
order. These include persistent dieting, usually driven by the
overevaluation of shape and weight; repeated checking of body
shape, which tends to magnify concerns about appearance; and re-
liance on aspects of the eating disorder (especially binge eating) to
cope with adverse moods.
Epidemiology
In the general population among women aged 16–​35  years, the
point prevalence of bulimia nervosa is between 1 to 2% and that of
the OEDs as high as 5%. Anorexia nervosa is much less common.
In clinical settings, the diagnostic distribution differs according
to age. Among adolescents, anorexia nervosa is the main presen-
tation, whereas among adults the OEDs and bulimia nervosa are
more common (Fig. 26.5.10.1). Nine out of ten adults with anor-
exia nervosa, bulimia nervosa, or an OED are female and most are
in their twenties. The demographic distribution of binge eating dis-
order is different in that most patients are middle-​aged and about a
third are male.
It is widely thought that eating disorders have become more
prevalent over recent decades, but other explanations are plausible,
including greater help-​seeking, better detection, and changes in
diagnostic practice.
Clinical features
Anorexia nervosa and bulimia nervosa, and most OEDs, share a
distinctive ‘core psychopathology’, the overevaluation of shape and
weight. Whereas most people evaluate themselves on their per-
ceived performance in a variety of domains of life (the quality of
their relationships; their work, and so on), people with eating dis-
orders judge their self-​worth largely, or even exclusively, in terms of
their shape and weight and their ability to control them. This psy-
chopathology is peculiar to the eating disorders and is rare in the
general population. Most features of these disorders are secondary
to this psychopathology and its consequences. For example, it re-
sults in a pursuit of weight loss and an intense fear of weight gain
and fatness, and it leads many patients to scrutinize their bodies
focusing on parts that they dislike. This may contribute to them
overestimating their size.
Anorexia nervosa
In anorexia nervosa, the pursuit of weight loss leads patients to en-
gage in a severe and selective restriction of food intake with foods
viewed as fattening being avoided. There is no true ‘anorexia’ (in
the sense of a loss of appetite). In the early stages undereating may
be a goal in its own right, the patient valuing the sense of self-​
control that it imparts. Some also engage in a driven type of exer-
cising which contributes to their weight loss. Self-​induced vomiting
and other extreme forms of weight control (such as the misuse of
laxatives or diuretics) are practised by a subgroup. Depressive and
anxiety symptoms, irritability, lability of mood, impaired concen-
tration, loss of sexual appetite, and obsessional features are fre-
quently present. Importantly these features get worse as weight is
lost and improve with weight regain. Interest in the outside world
also diminishes as patients become underweight with the result that
most become socially withdrawn and isolated. The patient does not
see their pursuit of weight loss as a problem and therefore has little
desire to change.
Bulimia nervosa
The eating habits of people with bulimia nervosa resemble those
seen in anorexia nervosa. The main distinguishing feature is that the
attempts to restrict food intake are punctuated by repeated episodes
Box 26.5.10.2  Principal risk factors for anorexia nervosa and
bulimia nervosa
General factors
•	 Female
•	 Adolescence and early adulthood
•	 Living in a Western society
Individual-​specific factors
Family history
•	 Eating disorder of any type
•	 Depression
•	 Substance abuse, especially alcoholism (bulimia nervosa)
•	 Obesity (bulimia nervosa)
Premorbid experiences
•	 Obstetric complications
•	 Adverse parenting (especially low contact, high expectations, parental
discord)
•	 Sexual abuse
•	 Family dieting
•	 Critical comments about eating, shape, or weight from family or
others
•	 Occupational or recreational pressure to be slim
Premorbid characteristics
•	 Low self-​esteem
•	 Perfectionism (anorexia nervosa and to a lesser extent bulimia
nervosa)
•	 Neuroticism
•	 Anxiety and anxiety disorders
•	 Obesity (bulimia nervosa)
•	 Early menarche (bulimia nervosa)
•	 Type 1 diabetes (bulimia nervosa)
BED
AN
BN
OEDs
Fig. 26.5.10.1  Typical distribution of the eating disorder diagnoses
among specialist adult outpatients.
AN, anorexia nervosa; BN, bulimia nervosa; BED, binge eating disorder; OEDs, other
eating disorders.
26.5.10  Eating disorders
6511
of binge eating. The frequency of these episodes ranges from once
a week (the diagnostic threshold) to several times a day, and the
amount eaten per episode is typically between 1000 and 2000 kcals.
In most cases, compensatory self-​induced vomiting or the taking of
laxatives or diuretics follows binge eating, but there is a subgroup of
patients who do not ‘purge’ in this way. The weight of most patients is
unremarkable as the effects of the undereating and overeating cancel
each other out. Depressive and anxiety symptoms are prominent ac-
companiments and a subgroup is prone to substance misuse or self-​
injury or both.
Other eating disorders
The other eating disorders are very similar to anorexia nervosa and
bulimia nervosa. There is the same overevaluation of shape and
weight, and the same tendency to engage in persistent and extreme
dieting and other forms of weight-​control behaviour. Most of the
OEDs are mixed states in which the features of anorexia nervosa and
bulimia nervosa are combined in such a way that it is not possible
to make either diagnosis. Body weight may be low if the dietary re-
striction is marked.
Many people with an OED have a history of anorexia nervosa or
bulimia nervosa, or both, reflecting the diagnostic migration that is
common among the eating disorders. The OEDs are as impairing as
bulimia nervosa.
Binge eating disorder
Binge eating disorder differs from the three other eating disorder
diagnoses. There is no tendency to engage in extreme weight-​control
behaviour and generally no overevaluation of shape and weight.
Instead, the binge eating occurs against a background of a general
tendency to overeat, much as in many cases of obesity. Indeed, many
people with binge eating disorder are overweight or have obesity.
The course of binge eating disorder is generally phasic rather than
persistent with extended periods, often lasting many months free
from the disorder.
Differential diagnosis
There is a long differential diagnosis of medical conditions that
can cause weight loss. The main psychiatric differential diagnosis
is weight loss due to severe depression. However, the diagnosis of
an eating disorder is best made on positive grounds using the his-
tory and mental state examination to detect the characteristic be-
havioural and attitudinal features, not by simply ruling out possible
physical causes.
Treatment
Detection and diagnosis
Many people with an eating disorder do not seek treatment. Those
with anorexia nervosa may not be aware that they have a problem or
they may attempt to hide it. Those with bulimia nervosa often keep
their problem secret. When people do present for treatment they
may do so only tentatively. Patients with anorexia nervosa typically
attend for help at the insistence of concerned others. Those suffering
from bulimia nervosa or an OED may attend of their own accord,
although often with physical complaints associated with the dis-
order such menstrual problems, infertility, or gastrointestinal dis-
turbance. Under these circumstances, making the correct diagnosis
can be difficult. The attitude and skill of the clinician during the
initial appointments is important as patients are easily put off from
re-​attending.
Place of treatment
Most patients are treated as outpatients. A few may require admis-
sion to a specialized eating disorders unit. Some may require admis-
sion to a medical unit.
Management of medical complications
Physical symptoms, signs, and abnormal laboratory investiga-
tions are often found in patients with anorexia nervosa (see Box
26.5.10.3). These are secondary to the disturbed eating habits and
the compromised nutritional state (especially low body weight)
and most are reversed by restoration of healthy eating habits and
sound nutrition. Treatment should focus on the eating disorder it-
self. It is, for example, inappropriate to treat starvation-​induced
hypothyroidism with thyroxine, and care is needed when correcting
chronic electrolyte disturbance.
Life-​threatening complications must be addressed and the
patient’s nutritional state optimized. Patients with a BMI less than
13 or who have lost weight at a rate of more than 1 kg per week
are at risk of death. They may require intensive nutritional support
as a medical inpatient, with monitoring of electrolytes and an elec-
trocardiogram. In such cases, collaborative management with a
psychiatrist skilled in the management of severe eating disorders is
essential. Behaviour intended to prevent weight gain may be very
challenging to manage on a medical ward and additional specialist
nursing may be required.
While oral refeeding is preferred, nasogastric tube feeding
may be needed. Patients with a BMI of less than 13 are at risk of
refeeding syndrome in which there is a potentially fatal shift in
fluids and electrolytes in response to unduly rapid refeeding. The
Mental Health Act can be used to treat life-​endangering starvation
as this is regarded as a manifestation of a mental illness.
One other chronic medical problem deserves particular mention.
This is the decrease in bone mineral density seen in longstanding
anorexia nervosa, which is associated with a substantially increased
fracture risk. Unlike the other medical complications, it may not
be fully reversed by the restoration of a healthy weight, adequate
diet, and the resumption of spontaneous menstruation. There is no
proven treatment for it.
Few physical abnormalities occur in bulimia nervosa unless
purging is frequent, in which case there is risk of electrolyte disturb-
ance. There are no medical complications of binge eating disorder
other than those secondary to comorbid obesity.
Management of the eating disorder
The main treatments are psychological and are delivered on an out-
patient basis. Various drugs influence the binge eating of patients
with binge eating disorder, but they are not widely used given the
effectiveness of psychological interventions.
SECTION 26  Psychiatric and drug-related disorders
6512
Drug treatment
There are no pharmacological treatments for anorexia nervosa. In
bulimia nervosa antidepressant medication may produce a decrease
in the frequency of binge eating, but it is not clear if this benefit
persists.
Psychological treatment
There is strong evidence supporting a specific form of cognitive be-
haviour therapy (CBT) for bulimia nervosa, which is endorsed by
many national clinical guidelines. Recently this treatment has been
superseded by an ‘enhanced’ version (CBT-​E) that can be used to
treat any form of eating disorder. It is a personalized treatment that
addresses the specific processes maintaining the individual patient’s
eating disorder (Box 26.5.10.4). Among non​underweight patients,
two-​thirds make a full response to CBT-​E, whatever their eating dis-
order diagnosis.
Treatment in those who are underweight (BMI <17.5) is more
difficult and not always successful. Psychological treatment with
CBT-​E may need to be lengthy. The response rate has yet to be firmly
established, but it appears to be approximately 40%.
In adolescent patients, a specific form of family therapy is the
favoured treatment with a response rate in the region of 50%. Binge
eating disorder responds well to a variety of psychological inter-
ventions including following a cognitive behavioural self-​help pro-
gramme with a limited amount of support.
Prevention
The research on prevention has mostly focused on programmes de-
signed to reduce concerns about body shape. The group targeted has
been adolescent girls and young women. While these programmes can
reduce shape concerns, it has not yet been demonstrated that this has
any effect on the likelihood of developing an eating disorder. Whether
this is the right strategy is a moot point as body image concerns are
only one among many risk factors for developing an eating disorder,
and the magnitude and universality of its contribution is not clear.
Outcome
Established eating disorders tend to persist without treatment.
Treatment-​seeking is often delayed and presentations may be
initially to medical services for physical complications of the
disorders.
•	 Electrolyte disturbance (varied in form; present in those who vomit
frequently or misuse large quantities of laxatives or diuretics):
vomiting—​metabolic alkalosis and hypokalaemia; laxative misuse—​
metabolic acidosis, hypokalaemia
Other abnormalities
•	 Enlarged cerebral ventricles and deceased cortical substance
•	 Osteopaenia and osteoporosis, especially of the spine (with height-
ened fracture risk)
Box 26.5.10.3  Principal medical complications of anorexia
nervosa and bulimia nervosa
Physical symptoms
•	 Heightened sensitivity to the cold
•	 Gastrointestinal
symptoms—​bloatedness,
constipation,
fullness
after eating
•	 Dizziness, palpitations, syncope
•	 Amenorrhoea (in females not taking an oral contraceptive); low sexual
appetite; infertility
•	 Poor sleep with early morning wakening
Physical signs
•	 Emaciation
•	 Stunted growth and failure of breast development (if prepubertal
onset)
•	 Dry skin; hair loss; fine downy hair (lanugo) on the back, forearms, and
side of the face
•	 Skin abrasions and callous formation on dorsal surface of the
hand (in those who use their fingers to induce vomiting; Russell’s
sign)
•	 Swelling of parotid and submandibular glands (especially in bulimia
nervosa)
•	 Erosion of inner surface of front teeth (perimylolysis) in those who
vomit frequently
•	 Cold hands and feet; acrocyanosis; hypothermia
•	 Bradycardia; hypotension; cardiac arrhythmias (especially in those
with electrolyte abnormalities)
•	 Dependent oedema (complicating the evaluation of body weight)
•	 Weak proximal muscles (elicited as difficulty rising from a squatting
position)
Abnormalities on investigation
Endocrine
•	 Low gonadotropin-​releasing hormone (GnRH), luteinizing hor-
mone (LH), follicle-​stimulating hormone (FSH), oestrogen, and
testosterone
•	 Low T3, T4 in low normal range, normal thyroid-​stimulating hormone,
TSH (‘low T3 syndrome’)
•	 Mild elevation of plasma cortisol
•	 Elevated growth hormone with increased IGF-​1
•	 Hypoglycaemia (uncommon)
Cardiovascular
•	 Electrocardiogram abnormalities (especially in those with electrolyte
disturbance)
•	 Reduced left ventricular mass
Gastrointestinal
•	 Delayed gastric emptying; delayed small bowel transit time
•	 Acute gastric dilatation (rare, secondary to binge eating or excessive
refeeding)
•	 Decreased colonic motility (secondary to chronic laxative misuse)
Haematological
•	 Moderate normocytic normochromic anaemia
•	 Mild leucopoenia with relative lymphocytosis
•	 Thrombocytopenia (uncommon)
Other metabolic abnormalities
•	 Hypercholesterolemia
•	 Hypophosphatemia (exaggerated during refeeding)
•	 Dehydration

26.5.11 Schizophrenia 6513 Stephen M. Lawrie
26.5.11 Schizophrenia 6513 Stephen M. Lawrie
26.5.11  Schizophrenia
6513
Anorexia nervosa
The course of anorexia nervosa varies greatly. In the early months
and years it may be self-​limiting; it may require some form of inter-
vention; it may evolve into bulimia nervosa, or another eating
disorder; or it may persist and become treatment-​resistant. It is par-
ticularly important to be aware that anorexia nervosa can be life-​
threatening. It has a standardized mortality ratio of about six, most
deaths being a direct result of medical complications related to star-
vation, or suicide.
Bulimia nervosa
Once fully developed, bulimia nervosa tends to be self-​perpetuating.
It may persist for years or even decades with adverse effects on self-​
esteem, career, and relationships. It is common for sufferers to delay
seeking help due to the shame associated with binge eating, and it
is easy for them to keep the problem secret as their eating in public
and appearance are both unremarkable. However, treatment—​when
sought—​is usually effective
FURTHER READING
Fairburn CG (2008). Cognitive behavior therapy and eating disorders.
Guilford Press, New York, NY.
Lock J, le Grange D (2013). Treatment manual for anorexia nervosa: a
family-​based approach. Guilford Press, New York, NY.
Mehler PS, Krantz MJ, Sachs KV (2015). Treatments of medical
complications of anorexia nervosa and bulimia nervosa. J Eating
Disord, 3, 15.
National Institute for Health and Care Excellence (NICE) (2017).
Eating disorders: recognition and treatment. NICE guideline [NG69].
https://​www.nice.org.uk/​guidance/​ng69
Palmer RL (2014). Helping people with eating disorders, 2nd edition.
John Wiley and Sons, Chichester.
Royal College of Psychiatrists (2014). Report CR189. MARSIPAN: man-
agement of really sick patients with anorexia nervosa, 2nd edition. https://​
www.rcpsych.ac.uk/​usefulresources/​publications/​collegereports/​cr/​
cr189.aspx
26.5.11  Schizophrenia
Stephen M. Lawrie
ESSENTIALS
Schizophrenia is typically a severe chronic mental illness with a
high morbidity and increased mortality. It has a complex aetiology
including a substantial genetic component. Its clinical features include
characteristic delusions and hallucinations. There are no diagnostic
tests. The differential diagnosis is from manic states, organic brain dis-
orders, and substance misuse. Whilst the management is complex,
antipsychotic drugs are effective in reducing symptoms. The overall
prognosis is poor; many patients live restricted lives and there is a high
rate of suicide. However, some patients return to normal functioning.
Importantly for physicians, people with schizophrenia die on average
10 years earlier than the general population, mainly because of car-
diac and cerebrovascular disease, which is often inadequately treated.
Introduction
A psychotic disorder is a mental illness characterized by hallucin-
ations and/​or delusions. Schizophrenia is a psychosis in which the
hallucinations are typically auditory and the delusions often of a bi-
zarre nature. The literal translation of schizophrenia from the Greek
is ‘split mind’. This refers to a splitting of mental functions, and has
nothing to do with a so-​called split personality.
Box 26.5.10.4  Principal characteristics of enhanced cognitive
behaviour therapy (CBT-​E)
Aims
i.	 To normalize eating habits and, if applicable, restore body weight
ii.	 To correct the mechanisms that have been maintaining the eating
disorder
iii.	 To protect against relapse
Format
One-​to-​one treatment (although significant others may attend certain
sessions if indicated).
Number of sessions:
•	 Non​underweight patients—​about 20 hour-​long sessions over
20 weeks. Initial sessions twice-​weekly.
•	 Underweight patients—​Extended to about 40 hour-​long sessions over
40 weeks. Initial sessions twice-​weekly.
Content
Personalized to match the processes maintaining the patient’s eating
disorder
Two versions:
•	 The focused version is the default version and is suitable for most pa-
tients. It focuses exclusively on the eating disorder features.
•	 The broad version is designed for a subgroup of patients in whom
certain characteristic problems outside the eating disorder are
maintaining the condition, namely extreme perfectionism, marked
low self-​esteem or major interpersonal difficulties.
Four stages:
•	 In stage 1, the focus is on gaining an understanding of the eating
problem and helping patients modify and stabilize their pattern of
eating. There is also emphasis on personalized education and the ad-
dressing of concerns about weight. The sessions are twice-​weekly.
•	 In stage 2, progress is systematically reviewed and plans are made for
the main body of treatment
•	 Stage 3 consists of a run of weekly sessions focused on the processes
that are maintaining the patient’s eating problem. Usually this involves
addressing concerns about shape and eating; enhancing the ability
to deal with day-​to-​day events and moods; and reducing dietary
restraint.
•	 Towards the end of stage 3 and in stage 4, the emphasis shifts onto
the future. The focus is on how to deal with setbacks and maintain
improvement.
SECTION 26  Psychiatric and drug-related disorders
6514
Aetiology
Genetic factors
Schizophrenia runs in families, but the monozygotic concordance
rate is only 50% (i.e. the environment clearly plays a significant
role). Most cases are likely to be multifactorial and polygenic. The
Psychiatric Genomics Consortium recently pooled data from more
than 36 000 cases and 100 000 controls and found 108 separate gen-
etic loci associated with an increased risk, accounting for about 7%
of the variance in liability. Each gene, however, only increases the
risk by 5% or less (Table 26.5.11.1). Some of the genes implicated
include those concerned with the major histocompatibility complex,
calcium signalling, glutamatergic, and dopaminergic neurotrans-
mission. There are however some rare genetic variants with larger
effects: a 22q11.2 micro-​deletion sometimes called DiGeorge syn-
drome or velo-​cardio facial syndrome increases the risk of schizo-
phrenia and other severe mental illnesses about 30 times. Recent
advances in genetic technology have allowed the identification of
other copy number variations which are deletions or additional
copies of genes. These are present in 2–​3% of people with schizo-
phrenia, and in people with autism and intellectual disability.
Environmental factors
There is an excess of winter births. This may convey risk by infection
or poor nutrition. Neurodevelopmental disruptions such as obstetric
complications and minor physical anomalies, motor, cognitive, and
social difficulties, all increase the risk of subsequent schizophrenia.
Urban birth and upbringing, and adversity in childhood, also in-
crease the risk. Chronic, regular use of cannabis and stimulants are
among the most potent risk factors for precipitating schizophrenia,
but the strongest known environmental risk factor is immigration,
possibly related to the perceived threat or lack of support in an alien
environment. Stressful life events may precipitate psychosis in those
who are predisposed. Stress, including negative ‘expressed emotion’
(criticism, hostility) from relatives, can also cause relapses.
Pathophysiology
All effective antipsychotic drugs block dopamine (D2) receptors,
and the potency with which they do that correlates with the dose
required in clinical practice. This provides indirect evidence for the
so-​called ‘dopamine hypothesis of schizophrenia’ which posits that
acute, positive symptoms are caused by increased dopamine turn-
over. This hypothesis is supported by strong evidence that dopa-
minergic agonists—​ephedrine, cocaine, and amphetamine—​can
cause psychosis. Direct evidence also comes from an impressively
consistent literature showing increased radiolabelled dopamine
precursor turnover in presynaptic neurons in the striatum. Acute
administration of dopamine agonists increases dopamine turnover
and positive psychotic symptoms. Cannabis and social stress may
also increase the risk of schizophrenia via release of dopamine.
There is, however, as much evidence for disruption in glutamate
neurotransmission in schizophrenia. A glutamate theory also offers
a better account of the cognitive disruption typically seen in schizo-
phrenia, including an average 10-​point drop in IQ from premorbid
levels.
It remains unclear just how these neurochemical disruptions re-
sult in the mental changes observed, such as delusions and hallu-
cinations. The hypotheses include disrupted dopamine signalling
making irrelevant stimuli abnormally salient, causing persecutory
delusions, and dysconnection in corollary discharges between lan-
guage regions of the cortex, causing auditory hallucinations.
Epidemiology
Schizophrenia has a modal age at onset of 25 years. It is usually asso-
ciated with long-​term disability. The prevalence is remarkably con-
sistent worldwide at approximately 0.5%. This translates to about
300 000 cases in the United Kingdom.
Clinical features
The diagnostic criteria in DSM-​5 are summarized in Table 26.5.11.2.
The ICD-​10 diagnostic criteria differ in that they continue to stress
the particular importance of Schneider’s’ ‘First Rank Symptoms’
(FRSs) in making the diagnosis. FRSs include certain types of audi-
tory hallucinations such as hearing one’s own thoughts spoken aloud
(‘echo de la pensee’), hearing voices that comment on what one is
doing or thinking (in the second person) or arguing about or dis-
cussing one in the third person. FRS also include specific delusions;
these include the conviction that thoughts from outside are being
inserted into one’s head (‘thought insertion’), that thoughts are being
withdrawn from one’s head (‘thought withdrawal’) and that one’s
thoughts are broadcast to others (‘thought broadcast’), ‘delusions of
passivity’ and feelings or volitions or bodily functions which are ex-
perienced as imposed by an outside force or agency.
The symptoms of schizophrenia may be divided into:
•	 Positive symptoms: these are pathological by their presence; for
example, hallucinations, delusions, disorganized speech (aka
‘thought disorder’, such as ‘loosening of associations’ between
ideas), and incongruity of affect (inappropriate laughter or tears).
Table 26.5.11.1  The main risk factors for schizophrenia
Family history
c.50 × increased risk in monozygotic twin of
person with schizophrenia
10 × increase in other first degree relatives
Immigrant status
c.5 × increased risk
Childhood adversity
c.3 × increased risk
Cannabis use (regular)
c.3 × increased risk
Table 26.5.11.2  Summary of DSM-​5 diagnostic criteria
for schizophrenia
A–​E are all required:
A. Two or more of: delusions, hallucinations, disorganized speech, grossly
disorganized behaviour, negative symptoms, for one month (less if treated)
B. Impaired social or occupational functioning
C. Illness continuous over at least six months (including acute phase)
D. Any mood disorder is only brief or minor
E. Not due to drugs of abuse, medication, or medical illness
26.5.11  Schizophrenia
6515
These tend to dominate the clinical picture in the acute phase and
respond to antipsychotic medication.
•	Negative symptoms: these are pathological by their absence; for
example, lack of affect, lack of motivation (avolition), poverty of
speech (alogia), and social withdrawal. Negative symptoms do
not tend to respond to current treatments, are a poor prognostic
sign and tend to dominate the clinical picture in chronic cases.
Differential diagnosis
To make a diagnosis of schizophrenia it is necessary to identify the
key features. This may take time and usually requires a collateral
history.
The main psychiatric differential diagnosis is from the manic
phase of bipolar disorder. In manic states the delusions are usually
is in keeping with mood (‘mood congruent’) and the mood disturb-
ance dominates the clinical picture.
The main medical differential diagnosis is from alcohol or illicit
drug misuse, and less commonly from organic psychoses resulting
from infections condition such as neurosyphilis, temporal lobe epi-
lepsy, and head injury. Impaired conscious level and fluctuating con-
fusion suggest an organic syndrome. Drug screening, appropriate
investigation, and brain scanning should be considered in all new
cases of acute psychosis.
Clinical investigations
Despite notable scientific progress in understanding the genetic
aetiology and pathophysiological mechanisms, there is no object-
ively measurable diagnostic abnormality; schizophrenia remains
diagnosed as a syndrome based on the clinical picture. However,
it has been known for years that patients with schizophrenia have
large lateral ventricles and reduced brain volumes, especially in
frontotemporal regions. Brain imaging technologies and studies
have advanced to the point that structural MRI in particular has
been found in research settings to provide an early diagnoses with
80–​90% overall accuracy, but such methods are not yet ready for
routine clinical use.
Treatment
Principles of management
Treatment with antipsychotic drugs is the mainstay of the treat-
ment of schizophrenia. They reduce behavioural disturbance
within minutes or hours, reduce acute symptoms in days, and
reduce the risk of relapse over months and years. The number
needed to treat (NNT) for response in each of these situations is
approximately three. Consequently antipsychotic drug treatment
for schizophrenia is among the most effective interventions in
medicine.
Antipsychotic drugs also have limitations, however. They are
more effective against positive than negative symptoms. They
also have unpleasant adverse effects. Some adverse effects such
as sedation can be useful in acute psychosis, but weight gain can
be major problem in chronic cases. The other major adverse ef-
fect is a range of extrapyramidal side effects. Acute dystonia such
as oculogyric crises, trismus, and torticollis can occur within
minutes or hours and may require parenteral procyclidene or
benztropine. Akathisia and parkinsonism may emerge after days
or weeks; while they respond to propranolol or anticholinergics,
respectively, they are better avoided by prescribing low doses of
antipsychotics in the first place. Tardive dyskinesia can emerge
after years of treatment, but is becoming less common. This may
reflect the increasing use of so-​called ‘second generation’ or ‘atyp-
ical’ antipsychotic drugs, which cause few extrapyramidal side ef-
fects but more weight gain than ‘first generation’ drugs such as
chlorpromazine and haloperidol.
As efficacy and adverse effects vary from drug to drug (Table
26.5.11.3), fine-​tuning of medication type and dose is needed to
optimize effectiveness, promote compliance, and reduce adverse
effects.
Behavioural, psychological, and social interventions are also ef-
fective for patients with schizophrenia and are popular with patients
and carers, but are inconsistently implemented. Support and illness
education can help patients and carers cope with what is usually a
chronic illness, and ‘family intervention’ may help to reduce relatives
‘expressed emotion’. Cognitive behavioural treatment (CBT) seems
likely to be useful in most phases of the illness, usually in addition
to antipsychotic medication, but the evidence base for this remains
controversial.
Typically, only 10% of people with schizophrenia will sustain
long-​term competitive employment, but 50% or so can manage with
vocational rehabilitation and ‘job coaches’. Both the so-​called ‘re-
covery movement’, which stresses that patients can lead satisfying
Table 26.5.11.3  Commonly used antipsychotic drugs
Type/​name of drug
Optimal dosea
Main side effects
Phenothiazines
Chlorpromazine
Thioridazine
Trifluoperazine
400–​600 mg/​day
400–​600 mg/​day
5–​10 mg/​day
Sedation
Anticholinergic
Extrapyramidal
Butyrophenones
Haloperidol
8–​12 mg/​day
Extrapyramidal
Benzamides
Sulpiride
Pimozide
800–​1200 mg/​day
8–​10 mg/​day
Minimal
Minimal
Depot injections
Flupentixol decanoate
Fluphenazine decanoate
Haloperidol decanoate
40 mg every 2 weeks
25 mg every 2 weeks
100 mg monthly
Extrapyramidal
Extrapyramidal
Extrapyramidal
Second-​generation drugs
Risperidone
Olanzapine
Quetiapine
Amisulpiride
4–​6 mg/​day
10–​15 mg/​day
300–​600 mg/​day
800–​1200 mg/​day
Extrapyramidal
Weight gain
Sedation
Agitation
Atypical antipsychotic drugs
Clozapine
300–​600 mg/​day
Hypersalivation
a This dose of chlorpromazine is established from meta-​analyses. Others are calculated
as chlorpromazine equivalents. These are less certain for depot, second-​generation, and
atypical drugs.
SECTION 26  Psychiatric and drug-related disorders
6516
and productive lives, and ‘early psychosis services’, offering holistic
care packages for those at risk of or in their first episode of psych-
osis, have improved the overall outlook for patients with acute and
chronic schizophrenia.
The stigmatization of patients with schizophrenia, and those who
look after them, remains common. The issue of violent behaviour in
particular is frequently misrepresented in the media. While there is
a slightly increased risk of violence in acute, unmedicated schizo-
phrenia, patients are much more likely to be assaulted that to assault
others. Mentally ill people commit less than 10% of all homicides;
the public are much more likely to be assaulted by family or friends
than by strangers with schizophrenia.
Acute treatment
Patients in an acute episode, especially if it is their first episode
or is associated with illicit drug use, may lack insight into their
condition. They may then require compulsory treatment using
the law. In the United Kingdom, this is usually under the Mental
Health Act.
Acute behavioural disturbance, such as agitation or aggression
may be treated with a combination of haloperidol (5 mg) and lor-
azepam (2 mg). The subsequent regular drug treatment should usu-
ally be with a low-​potency first generation antipsychotic drug such
as chlorpromazine (at a dose of 400–​600 mg daily), or a second-​
generation antipsychotic drug such as risperidone (4–​6 mg daily)
or olanzapine (10–​15 mg daily). Most patients will respond to one
or other of these.
With the reduction in the numbers of psychiatric beds, there is
an emphasis on treatment outside of hospital. Community services,
‘crisis teams’ and ‘intensive home treatment teams’ are often, but not
always, able to manage patients in their homes with frequent visits
for monitoring and support.
Maintenance treatment
Numerous randomized trials have found that maintenance use of
antipsychotic medication reduces relapse rates at over one year com-
pared to placebo (drugs 27% vs. placebo 64%; number needed to
treat 3). A smaller dose of antipsychotic drug is often sufficient for
maintenance and may enhance compliance.
Esterified preparations of antipsychotic drugs allow them to be
given as slow releasing fat-​soluble depot injections every two to four
weeks for patients who want that (rather than taking pills every day),
or for those who need to be treated against their will.
Approximately one-​third of patients will not adequately respond
to first-​ or second-​line treatments. They should be offered the only
truly ‘atypical antipsychotic drug’, clozapine (300–​600  mg daily).
This works in most patients with such ‘treatment-​resistant schizo-
phrenia’, but requires regular blood monitoring to reduce the risk of
agranulocytosis.
Various psychological and social interventions including cogni-
tive behavioural treatment, illness education, and family interven-
tion can reduce the relapse rate. Members of the multidisciplinary
community mental health teams can provide these and other
services. For example, community psychiatric nurses can monitor
and support patients, give depot injections, and help patients access
other services. Social workers can help with benefits and inde-
pendent or supported accommodation.
Outcome
Some people with schizophrenia have manifest difficulties in their
development, but most have had an unremarkable childhood.
The first symptoms are usually a prodromal ‘loss of (mental) con-
trol’, anxiety, or depression over months or years before the ad-
vent of delusions and hallucinations in early adulthood. Major
behavioural changes can accompany the development of delu-
sions and hallucinations. Relapses and remissions with some re-
sidual disability are typical, and complete lasting recovery is rare.
Good treatment response is predicted by a good initial response to
medication, but most patients will have a relapsing and remitting
illness course, with some ongoing negative symptoms, intermittent
positive symptoms, social and occupational impairments between
episodes.
Predictors of outcome
Acute onset and good premorbid functioning predict a better prog-
nosis. Living in a developing country may be associated with a better
overall outcome, possibly because of greater social support. Five to
ten per cent (5–​10%) of patients with schizophrenia will commit
suicide.
Medical morbidity
Most people with schizophrenia die of heart attacks, cancer, and
strokes, and they do so approximately 10–​15 years earlier than
population average. This shortened life expectancy is attribut-
able to both behaviour and circumstance; most patients smoke
heavily and many drink to excess. These effects are compounded
by poverty and poor diet and inactivity. There is a major med-
ical challenge in correcting the current underinvestigation and
undertreatment of these serious medical conditions in people
with schizophrenia.
FURTHER READING
Howes OD, Murray RM (2014). Schizophrenia: an integrated socio-​
developmental-​cognitive model. Lancet, 383, 1677–​87.
Leucht S, et al. (2012). Antipsychotic drugs versus placebo for relapse
prevention in schizophrenia: a systematic review and meta-​analysis.
Lancet, 379, 2063–​71.
Schizophrenia Working Group of the Psychiatric Genomics
Consortium (2014). Biological insights from 108 schizophrenia-​
associated genetic loci. Nature, 511, 421–​7.
Turner DT, et al. (2014). Psychological interventions for psychosis: a
meta-​analysis of comparative outcome studies. Am J Psychiatry, 171,
523–​38.
Zarogianni E, Moorhead TW, Lawrie SM (2013). Towards the identi-
fication of imaging biomarkers in schizophrenia, using multivariate
pattern classification at a single-​subject level. Neuroimage Clin, 3,
279–​89.

26.5.12 Somatic symptom and related disorders 6517
26.5.12 Somatic symptom and related disorders 6517 Michael Sharpe
26.5.12  Somatic symptom and related disorders
6517
26.5.12  Somatic symptom and
related disorders
Michael Sharpe
ESSENTIALS
Somatic symptom disorder is a diagnosis for patients who have
marked concern about physical symptoms that appears to be dis-
proportionate to the severity of any associated disease. In conver-
sion disorder the patient’s symptom is loss of a function, such as
movement of a limb. This does not mean that the symptoms are not
real. Somatic symptom disorder incorporates the older diagnoses
of somatoform disorder, somatization disorder, Briquet’s syndrome,
and hypochondriasis.
Somatic symptom disorder of mild severity is common in medical
clinics; it usually responds to simple explanation and reassurance.
More severe somatic symptom disorder with multiple symptoms and
severe disability is less common, but important to diagnose because
these patients are at substantial risk of iatrogenic harm from excessive
investigation and speculative medical or surgical treatment. Severe
somatic symptom disorder usually requires multidisciplinary care,
including liaison psychiatry.
Introduction
There are several psychiatric diagnoses specifically applicable to
patients who present with concern about symptoms that is dis-
proportionate to the severity of any physical disease. This dif-
ferential diagnosis is considered in the chapter on medically
unexplained symptoms. While the most commonly associated
psychiatric diagnoses are depressive and anxiety disorders, this
chapter focuses on patients whose presentations are not ad-
equately explained by either physical disease or by depressive or
anxiety disorders.
Somatic symptom disorder (SSD) is a new term which in-
cludes syndromes previously referred to as somatoform dis-
orders, somatization disorder (or Briquet’s syndrome) and
hypochondriasis. The core feature of these disorders is that the
patient’s reaction to their physical symptoms is the focus of clin-
ical concern. Common physical symptoms of somatic symptom
disorders are pain and fatigue, although almost any symptom
may be the focus of attention. The symptoms may cluster to-
gether in apparent association with a particular bodily system
such as musculoskeletal pain, bowel-​related symptoms, or chest
pain. In more severe cases, symptoms are typically diverse and
relate to multiple bodily systems.
Simply having physical symptoms does not merit a diagnosis of
SSD, even if these symptoms are unexplained by physical disease.
A  diagnosis of SSD requires that additional features are present.
These include excessive concern or preoccupation with the symp-
toms, associated emotional distress, and maladaptive behaviour
in relation to the symptoms such as the repeated and unnecessary
seeking of medical attention. Patients with severe SSD are commonly
very disabled, receive large amounts of unproductive medical atten-
tion, and suffer iatrogenic harm.
A related disorder is called conversion disorder (or functional
neurological symptom disorder). This is similar to SSD, but in this
disorder the patient’s complaints include apparent loss of or change
in a function, such as movement of a limb or impairment of vision.
It also includes attacks that look like epileptic seizures but are not
(so-​called non​epileptic attacks), gait disorders, and other abnormal
movements.
Aetiology
The aetiology of SSD is multifactorial. Predisposing factors for se-
vere SSD include a family history, childhood neglect and abuse,
and childhood experience of illness in the family. Symptoms may
be associated with depression and anxiety. An ongoing interaction
with medical services is probably a maintaining factor, with the
patient increasingly developing the conviction that they are sick,
even in the absence of medical evidence for this belief. The patient’s
life may become focused on care-​seeking and disability, behaviour
that may be reinforced by family members, partners, and others.
Particularly important is the behaviour of doctors who may ex-
acerbate the disorder. Ways in which this may happen are listed in
Box 26.5.12.1.
These iatrogenic factors are particularly important to consider, as
even if we cannot always successfully treat a patient with severe SSD,
we can at least avoid making the problem worse.
Epidemiology
Physical symptoms are extremely common in the general popu-
lation, but only a few people experiencing them will seek medical
attention, usually because of concern about the cause or because
of severe discomfort or disability. The prevalence of SSD will vary
by setting, but is more common in specialist clinics where it may
account for 10–​20% of consultations. Severe SSD, previously termed
somatization disorder or Briquet’s syndrome, in which there is a
lifelong history of multiple symptoms and usually severe associated
disability, is present in about 5% of medical patients. While only a
small number of patients with SSD become inpatients, when this
Box 26.5.12.1  Potential psychological iatrogenesis in somatic
symptom disorder
•	 Inadvertently exacerbating the patient’s concern (e.g. by mentioning
rare diseases or ordering unnecessary tests)
•	 Dismissing the patient’s complaints, which may lead them to reject the
reassurance given
•	 Giving inappropriate advice such as recommending excessive resting
or unnecessary splints and supports, which may only serve to increase
attention on the complaint and cause unwanted effects such as muscle
weakness
•	 Providing inappropriate disease focused pharmacological and sur-
gical interventions, which may only generate further symptoms (e.g.
abdominal surgery causing adhesions and opiate prescribing causing
addiction)
SECTION 26  Psychiatric and drug-related disorders
6518
occurs it carries a high risk of iatrogenic harm, for example, from
unnecessary surgery.
Clinical features
The main features of SSD are physical symptoms and the patient’s
concern about these. There may be no identifiable disease. If there is
disease, the patient’s concerns are markedly disproportionate, usu-
ally focusing on the symptoms themselves and their distressing or
disabling quality, although sometimes their main worry is about the
possibility of undiagnosed serious disease that persists despite med-
ical evidence to the contrary. Such patients may repeatedly seek re-
assurance from doctors.
SSD may be mild, moderate, or severe. In mild cases, there
may only be one or two symptoms, such as pain and fatigue. In
moderate cases, there may be multiple symptoms associated with
distress and disability, and often frequent and unproductive inter-
actions with doctors. Patients with severe cases may have lifelong
multiple symptoms and severe disability, for example, being
wheelchair bound. For patients with severe SSD, pointers to the
diagnosis may be apparent even before the consultation. The GP
referral letter and medical records may note frequent attendance
at medical services with a long history of numerous negative (and
often repeated) investigations. There may also be a history of failed
treatment with a record of multiple symptom-​relieving medica-
tions and even surgery.
Differential diagnosis
The differential diagnosis is from other medical and psychiatric
conditions.
Medical conditions
The main medical differential is from symptoms that are entirely at-
tributable to disease. It should be noted, however, that the identifi-
cation of disease does not necessarily exclude SSD. For example, a
high proportion of patients with non​epileptic attacks (attacks that
look like epilepsy but are not associated with seizure activity in the
brain) also have electroencephalogram (EEG) diagnosable epilepsy.
The coexistence of SSD and a diagnosis of potentially fatal disease,
for example, when the patient has both non​cardiac chest pain and
severe coronary artery disease, greatly increase the complexity of
management.
Other psychiatric disorders
Other psychiatric disorders are associated with severe concern about
physical symptoms. Anxiety disorders, especially panic disorder,
can cause physical symptoms (breathlessness, paraesthesia, chest
pain, and dizziness). Depressive disorder can also be the cause of
troublesome physical symptoms, such as lethargy, sleep disturbance,
pain, and weight loss. These symptoms may lead both the patient
and their physician to erroneously conclude that they have a medical
condition. It is important to diagnose anxiety and depression as they
are relatively easily treated.
Occasionally, concern about somatic symptoms may be delu-
sional and part of a psychotic illness, for example, a patient who is
unshakably convinced that a burning sensation in his head is due to
tearing of his brain.
Factitious disorder and malingering
Patients with SSD suffer and should be differentiated from patients
who construct medical presentations in order to deceive doctors.
While such deliberate faking of symptoms and signs certainly oc-
curs, it is unusual in routine clinical practice. Clues to its presence
are observations or reports of markedly inconsistent behaviour (e.g.
a patient who attends in a wheelchair but who is later seen walking
briskly to their car or playing tennis). In such cases, if the patient’s
apparent aim is the seeking of medical care and attention, the diag-
nosis is that of factitious disorder, severe cases of which have been
referred to as ‘Munchausen’s syndrome’. If the apparent aim is to seek
other forms of benefit such as financial compensation or exemption
from a duty or prosecution, the behaviour does not merit a psy-
chiatric diagnosis: it is a form of dishonest behaviour, often called
malingering.
Clinical assessment
The history and medical records are often critical to the diagnosis
by documenting a history of consulting and negative investiga-
tions. While the patient must be assessed for physical disease in the
usual way, care should be taken about unnecessarily repeating or
duplicating investigations. It is uncommon to miss serious physical
disease if a careful clinical assessment is made.
History
The history should include not only questions about symptoms, but
also questions about the patient’s fears and beliefs about the symp-
toms, their emotional reaction to them, and how they cope. The his-
tory of previous illness may reveal long-​standing similar symptoms
that have been extensively investigated. A full list of medications the
patient takes is important; it may be a long and illogical one.
Physical examination
It is important to physically examine the patient. This may not only
reveal unsuspected clinical signs suggesting disease, but also helps
to reassure the patient that their complaints have been taken ser-
iously and properly assessed. It may also reveal scars from many
previous operations. In conversions disorder, positive findings on
neurological examination help in making the diagnosis, for ex-
ample, Hoover’s sign (demonstration of synergistic contraction,
e.g. if a patient is asked to raise their right leg off the bed, they will
naturally tense the extensors of their left leg as they do so; if they
don’t, then they are not making a genuine effort, and Hoover’s sign
is positive).
Observations during the consultation
The patient with severe SSD may be disproportionately disabled,
even being pushed in a wheelchair or using braces. The patient
may moan or rub the affected bodily parts, as if to emphasize their
26.5.12  Somatic symptom and related disorders
6519
suffering. The patient’s partner may be seen to behave in a solicitous
way in keeping with the disproportionate disability.
Investigations
A balance must be struck between the risk of missing disease and the
iatrogenic psychological harm that can result from overinvestigation.
It is good practice to check if any investigation has been performed
recently before ordering it again.
Review of medical records
It is especially important to obtain and review all the medical re-
cords. These may indicate many previous assessments and investiga-
tions, as well as failed treatments. They may also document a pattern
of referral to many different specialists.
Management
The general principles of management are outlined in Box 26.5.12.2.
Acknowledging, reassuring, and explaining
The starting point of effective management is to make it clear to
the patient that you accept the reality of their suffering and do not
think they are imagining their symptoms. The patient then needs
reassuring that there is no evidence they have an unpleasant disease,
followed by a positive diagnosis and a credible explanation for their
symptoms and practical plan.
Providing reassurance
The provision of appropriate reassurance is an important part of the
medical consultation. To be effective it must be based on the patient’s
specific concerns, not those of the doctor, hence it is important to
ask the patient what they are worried they have before reassuring
them that they do not have it.
Many patients report the physical examination as particularly re-
assuring. A detailed explanation of what any investigations show can
also help, including showing the patient any relevant images.
While it is unwise to state categorically to any patient that they
have no disease, it can help to explain that the probability they have
the disease that they fear is very low, and why. Beware, however, of
the patient who repeatedly asks for reassurance about the same dis-
ease; they may have health anxiety disorder, a condition that is per-
petuated by repeated reassurance-​seeking.
Giving a diagnosis and explanation
Patients benefit from a positive diagnosis, and the failure to offer
one may set them off on an unhelpful search. However, the diag-
nosis given must be appropriate. The term ‘functional symptoms’
(symptoms that reflect a reversible change in bodily function rather
than fixed ‘structural disease’) may be useful here. This diagnosis
can then be elaborated with an explanation of what may have caused
the symptoms. While our understanding of the aetiology of SSD is
imperfect, we do have some evidence as described in the previous
section on aetiology. Explanations that include both psychological
and biological factors and emphasize which of these factors are po-
tentially reversible set the scene for treatment (see next).
It is worth noting that overly simplistic explanations for symp-
toms are probably unhelpful. On the one hand saying that the symp-
toms are ‘just psychological’ or ‘all in the mind’ is likely to offend the
patient and to reduce their confidence in you and your suggested
management plan. On the other hand, colluding with beliefs that
their symptoms indicate an untreatable disease (such as chronic
Lyme disease) when they do not is also likely to make the patient
unwilling to accept appropriate treatment and to promote unneces-
sary invalidity.
Giving practical advice
After the diagnosis and explanation, a positive plan of action that
specifies both what the patient can change and what the doctor will
do is required.
The patient can be advised how to change any potential illness-​
perpetuating behaviours (e.g. by becoming more active and not
searching for illnesses on the internet). The doctor can offer to
provide accurate information about the illness, review their pro-
gress and if appropriate prescribe (e.g. an antidepressant drug)
and refer (e.g. to physiotherapy or specialist psychology). Writing
specifically to the patient, as well as to the general practitioner to
summarize the conclusions of the medical assessment and the pro-
posed plan of action usefully reinforces these messages, which may
otherwise be forgotten, and gives the patient something to show
family members.
Antidepressant drug treatment
The so-​called antidepressant drugs have been found to be of some
benefit in SSD. While they are most likely to be helpful when the
patient is depressed or anxious, they can also reduce symptoms such
as pain in patients who are not depressed or anxious. However, an
observed high drop-​out rate from treatment emphasizes the need
for careful explanation and follow-​up to ensure adherence. For
these drugs to be accepted by the patient, a clear explanation of why
they are being prescribed is required. One of the following two ap-
proaches is suggested: the first is to explain that the term ‘antidepres-
sant’ is a misnomer and that the drugs are actually broad-​spectrum
agents of proven value for symptoms such as difficulty sleeping and
pain, as well as for depression. The second is to be explicit that they
are being prescribed for depression or anxiety, but to emphasize that
these psychological problems are an entirely understandable reac-
tion to the distressing somatic symptoms.
Box 26.5.12.2  Management principles for somatic symptom
disorder
•	 Exclude disease, but avoid unnecessary investigation or medical
referral
•	 Tell the patient that you accept and sympathize with their complaint(s)
•	 Give the patient a positive diagnosis and explanation
•	 Encourage a return to normal functioning
•	 Consider prescribing antidepressant drugs with appropriate
explanation
•	 Consider referral to specialist liaison psychiatry or psychology

26.5.13 Personality disorders 6520 Iain Jordan
26.5.13 Personality disorders 6520 Iain Jordan
SECTION 26  Psychiatric and drug-related disorders
6520
Psychological treatment
The most widely used psychological treatments for SSD are behav-
ioural or cognitive behavioural therapy (CBT). These therapies aim
to help the patient change the thinking (cognitions) and ways of
coping (behaviour) that are perpetuating their symptoms and asso-
ciated concerns. Systematic reviews of CBT have found it be to mod-
erately effective in SSD, but the psychological treatment of severe
cases of SSD requires considerable expertise.
Referral
Reasons to refer patients with possible SSD include diagnostic un-
certainty and the need for specialist management. Liaison psychiat-
rists can be helpful both in reaching a positive diagnosis of SSD and
in addressing the psychiatric differential diagnosis. Specialist med-
ical services may be available for the treatment of particular symp-
toms, for example, for chronic pain or chronic fatigue syndrome.
Specialist psychology services may be able to offer cognitive behav-
ioural therapy for SSD.
How to refer
When explaining the referral to the patient, it is wise to be positive
about the service you are referring to. If you are referring them to a
psychiatry or psychology service it is important to emphasize that
the referral does not mean you regard the patient’s symptoms as
‘not real’ or ‘all in the mind’. A patient is more likely to attend the
service to which you have referred if you say: ‘I see you have real
and troublesome symptoms. I am pleased to tell you that I can’t find
any evidence of serious disease but I am sorry to say that I do not
have a simple cure that I can prescribe. However, I can recommend
and refer you to a specialist service for your problem’, than if you
tell them: ‘There is clearly nothing wrong with you; it must all be
in your mind. There is nothing to do now but to refer you to the
shrinks.’
Management of severe SSD
Patients with complex and severe SSD pose particular management
challenges. They may seek care from multiple doctors and be per-
plexing and challenging to manage, especially if they also have a
serious medical condition. The help of a liaison psychiatrist should
be sought early and a management plan agreed with all concerned,
including the patient’s primary care physician if possible. This is often
best achieved by holding a case conference. The agreed plan should
limit referrals and investigations and include proactive regular re-
view of the patient, if possible by a single physician. Although
time-​consuming in the short term, this approach can both reduce
iatrogenic harm and save time and resources in the longer term.
Prognosis
The prognosis of SSD will depend both on the nature of the patient’s
presentation and how it is managed. Untreated, the prognosis for pa-
tients with SSD severe enough to be referred to secondary care is not
good, particularly if the disorder is not well managed. The prognosis
is best for those patients who were well before the onset of symptoms
and who have clear depressive and anxiety symptoms. It is worst for
those patients with very long-​standing multiple symptoms.
Areas of uncertainty and controversy
Many aspects of the nature and management of SSD are controver-
sial. The core issue is whether it is best regarded as a psychiatric/​
psychological problem or as a medical condition, with the risk that
the patient may end up abandoned in a medical ‘no man’s land’. This
problem has been played out particularly prominently in the de-
bate over the chronic fatigue syndrome/​myalgic encephalomyelitis.
A consideration of the changing medical fashions for the explan-
ation of such symptoms over the last few hundred years should en-
courage humility and suggests that current controversies may tell us
more about the inadequacies of our conceptualization of illness and
our health services than they do about our patients.
FURTHER READING
American Psychiatric Association (2013). Somatic symptom and re-
lated disorders. In: Diagnostic and stastical manual of mental dis-
orders, 5th edition (DSM-​5). American Psychiatric Association,
Arlington, VA.
Dimsdale JE, et al. (2013). Somatic symptom disorder: an important
change in DSM. J Psychosom Res, 75, 223–​8.
Kroenke K (2014). A practical and evidence-​based approach to
common symptoms: a narrative review. Ann Int Med, 161, 579–​86.
Sharpe M (2013). Somatic symptoms: beyond ‘medically unexplained’.
BJ Psych, 203, 320–​1.
Stone J, Carson A, Sharpe M (2005). Functional symptoms and signs in
neurology: assessment and diagnosis. J Neurol Neurosurg Psychiatry,
76, i2–​12.
Stone J, Carson A, Sharpe M (2005). Functional symptoms in neur-
ology: management. J Neurol Neurosurg Psychiatry, 76, i13–​21.
26.5.13  Personality disorders
Iain Jordan
ESSENTIALS
People have characteristic ways of perceiving, thinking about, and
responding to the world around them that are relatively stable over
time and across situations; this is referred to as their personality.
A diagnosis of personality disorder is made when the personality
is extreme and maladaptive and causes difficulty or distress to the
person themselves or to others. People with personality disorders are
often encountered in medical settings, which may be because they
have self-​harmed, suffered problems from drug or alcohol use, or
been injured because of unwise behaviour. Personality disorders also
complicate the medical management of medical conditions, for ex-
ample, by non​adherence to recommended treatment. The effective
short-​term management of personality disorders in medical settings
requires: (a) recognition of the diagnosis; (b) creation of a manage-
ment plan; and (c) consistent response to the problematic behav-
iours adhered to by all relevant staff.
26.5.13  Personality disorders
6521
Introduction
Everyone develops their own way of perceiving, thinking about, and
relating to the world that is stable over time and across situations,
which we call personality. Personality is a summary description of
the pattern of these traits in an individual. Personality is usually ap-
parent by mid-​adolescence and remains relatively stable thereafter.
At times of stress specific personality traits such as impulsiveness or
suspiciousness may become more noticeable.
Personality may be regarded as disordered when the traits are ex-
treme and problematic, leading to distress and difficulty for the af-
fected person and/​or those who interact with them.
Diagnostic classifications for personality disorder list many dif-
ferent types. These are conventionally grouped into three clusters
(see Table 26.5.13.1):
•	 Cluster A (eccentric) includes paranoid, schizoid and schizotypal
personality disorders;
•	 Cluster B (dramatic) includes antisocial (also called psychopathic
or dissocial), borderline (also called emotionally unstable), histri-
onic and narcissistic personality disorders;
•	 Cluster C (anxious) is composed of avoidant (also called anxious),
dependent, and obsessive-​compulsive personality disorders.
Describing personality disorders in a categorical way provides a
useful shorthand but is artificial as personality traits and personality
disorders are dimensional, meaning that the traits merge both into
one another and into normality.
Aetiology
The aetiology of personality disorders is a result of an inter-
action of genetic and environmental factors. There is evidence
that genetic factors contribute both to personality traits such as
impulsivity, neuroticism, and extraversion, and to personality
disorders, especially obsessive-​compulsive and dissocial types.
Environmental factors such as early childhood experiences and
adverse experiences such as neglect and abuse are also important
contributors.
Epidemiology
By definition, the onset of personality disorder is in adolescence or
early adulthood, although individuals may not come to the attention
of medical services until later in their life when circumstances lead
to an exacerbation of the resulting difficulties. Studies of the general
population report prevalence estimates 4–​22%, depending on the
definition of disorder. They also suggest that the overall prevalence
is similar in males and females.
Clinical features
The main features of the different types of personality disorders are
described in Table 26.5.13.1. Clinicians working in general hospitals
may encounter patients with personality disorders in several ways
(see Box 26.5.13.1).
In the emergency department, personality disorder is commonly
associated with self-​harm, injury because of combative, chaotic, or
abusive relationships and disturbed behaviour, or because of sub-
stance misuse.
In inpatient and outpatient settings, personality disorder may
manifest as non​compliance with treatment, unusual behaviour, and
extreme emotional responses to events or as abnormal relationships
Table 26.5.13.1  Features of specific personality disorders
Cluster
Specific
personality
disorder
Features
A
Paranoid
Distrust and suspicion of others
Bears grudges
Perceives threats and attacks on character or
reputation
Reluctant to confide in others
Schizoid
Detached, emotionally cold
Little interest in social relationships
Restricted range of activities
Indifferent to praise or criticism
Schizotypal
Odd beliefs, behaviour, or speech
Unusual perceptual experiences
Suspiciousness
Acute discomfort with close relationships
B
Antisocial
Disregard for rights of others
Deceitfulness, irresponsibility
Impulsivity, aggression
Lack of remorse
Borderline
Unstable personal relationships
Impulsivity, recurrent self-​harm, and suicidal
behaviour
Chronic feelings of emptiness, marked reactivity
of mood
Frantic efforts to avoid abandonment
Histrionic
Excessive emotionality and attention-​seeking
Inappropriate provocative behaviour
Suggestible
Theatrical, uses physical appearance to draw
attention
Narcissistic
Grandiosity, need for admiration
Preoccupied with fantasies of unlimited success
or brilliance
Sense of entitlement, believes self to be special
Lack of empathy, exploits others to achieve own
ends
C
Avoidant
Socially inhibited, avoids activities with others
Feelings of inadequacy, fear of being shamed or
ridiculed
Views self as socially inept
Preoccupied with being rejected
Dependent
Excessive and pervasive need for advice and
reassurance
Goes to excessive lengths to obtain nurturance
and support
Feels helpless when alone
Submissive, fears separation
Obsessive-​
compulsive
Preoccupation with orderliness
Perfectionism that interferes with task
completion
Overly scrupulous and inflexible
Unable to discard objects
SECTION 26  Psychiatric and drug-related disorders
6522
with staff. It is the nature of personality disorder that clinical staff
may find themselves behaving differently toward the affected pa-
tient. For example, they may have unusually strong emotional re-
actions to such patients, both negative and positive. They may also
treat them differently, for example, by booking additional consult-
ations or avoiding conversations with them.
Case examples
Case 1. A 22-​year-​old woman presents to the emergency depart-
ment after taking an overdose. She felt rejected by her boyfriend
who had not called her for three days. She has taken multiple over-
doses in the past and reports being sexually abused by her uncle.
The clinical team are split into those who feel very sorry for her
and those who consider her actions irresponsible and wasteful
of healthcare resources. The diagnosis is borderline personality
disorder.
Case 2. A 45-​year-​old man has been admitted to hospital for a
knee arthroscopy. He calls the nursing staff every 20 minutes for
pain relief or to ask their advice about whether he should have
the operation. He telephones his partner repeatedly to seek re-
assurance and becomes inconsolable when he cannot reach them,
fearing he will be left to take care of himself. The diagnosis is de-
pendent personality disorder.
Differential diagnosis
The main differential diagnosis of personality disorders is a normal
personality under stress (adjustment disorder). Other differentials
include exacerbation of normal personality traits due to depression,
psychotic disorders such as schizophrenia or delusional disorder
(especially for the cluster A personality disorders), bipolar disorder
(especially for borderline personality disorder), altered personality
due to a medical disorder (for examples, see Box 26.5.13.2), and
substance misuse disorders.
Assessment
Care should be taken in diagnosing someone with a personality dis-
order. The diagnosis may have long lasting negative consequences
for the patient and may be misused to apportion blame solely to
them for any difficult clinical interactions. While personality dis-
order often contributes to difficult interaction with doctors, such
difficulties may also reflect a variety of factors unrelated to the
patient’s personality.
It is consequently important to distinguish long-​term, stable, mal-
adaptive personality traits that have been present since adolescence
or early adulthood from transiently severe disturbances of behav-
iour. The diagnosis requires an assessment of personality traits and
functioning over the long term and in many different situations,
thus it is often necessary to obtain collateral information from other
people such as their friends, family, and primary care physician.
While the diagnosis of personality disorder requires that the
patient’s behaviour is not better explained by another mental dis-
order, it is important to note that many patients with personality
disorders also have comorbid mental conditions, for example,
depression, anxiety disorders, and substance misuse disorders.
Assessment for the presence of these comorbid disorders is im-
portant as treatment of them may improve the patient’s behaviour. It
is also important to assess any risk that the patient with personality
disorder may pose to themselves and to others.
If a diagnosis of personality disorder is made, the following should
be specified:
•	 The behaviour upon which this is based.
•	 The specific personality disorder type (or a cluster level diagnosis
given with the relevant elements of each specific personality dis-
order described, for example, if the patient has a cluster A type
personality disorder with elements of borderline and antisocial
personality disorders).
•	 It can be helpful to also note positive as well as negative person-
ality attributes.
•	 Situations or stressors that are recurrently problematic for the
person should be described along with their typical response
(e.g. feelings of abandonment after discharge from medical care
leading to self-​harm).
Treatment
An adult’s personality cannot, by definition, be substantially altered.
The overall aim of treatment for personality disorders is therefore to
help the patient to be aware of their most problematic personality
traits, to identify the stressors that lead to difficulties, and to develop
better strategies to manage them.
Box 26.5.13.1  Modes of presentation of personality disorder
to the general or specialist physiciana
•	 Emotional distress
•	 Self-​harm, including non​fatal self-​harm and suicide attempts
•	 Interpersonal conflict manifest in medical consultations or on
the wards
•	 Substance misuse
•	 Multiple medically unexplained symptoms
•	 Consequences of chaotic lifestyle/​impulsivity/​interpersonal problems
•	 Victim or perpetrator of violence or abuse (e.g. through the criminal
justice system)
•	 The medical consequences of impulsivity and intoxication
a Note that these presentations are not specific to individuals with personality
disorder.
Box 26.5.13.2  Examples of medical disorders which may cause
personality change
•	 Central nervous system neoplasms (primary or metastatic)
•	 Cerebrovascular disease
•	 Epilepsy
•	 Huntington’s disease
•	 Hypothyroidism
•	 Infections affecting the central nervous system
•	 Paraneoplastic syndromes
•	 Traumatic brain injury
26.5.13  Personality disorders
6523
The specific aims of treatment depend on the type of personality
disorder and the associated problematic perceptions, thoughts,
and ways of coping. They may include reducing emotional dis-
tress, improving compliance with medical treatment, stopping
self-​harming behaviour, and in the case of antisocial personality
disorder, reducing the risk of aggressive behaviour. The treatment
of coexisting psychiatric disorders, including substance misuse, is
important as such comorbidity can greatly exacerbate problematic
behaviour in people with a personality disorder.
Several psychological treatments are used to treat people with per-
sonality disorder. These include behavioural therapy, dialectic be-
haviour therapy, cognitive analytic therapy, psychodynamic therapy,
and therapeutic community-​based approaches.
Dialectic behavioural therapy (see Box 26.5.13.3) is used for the
treatment of so-​called borderline or emotionally unstable person-
ality disorder. It includes individual therapy (focused on the reduc-
tion of self-​harming behaviour and improvement in quality of life),
group-​based skills training (focused on increasing tolerance of dis-
tress, improving interpersonal relationships, regulating emotions,
and mindfulness) and telephone contact at times of crisis.
There is a limited role for drug treatment of personality disorder.
There is some evidence for the use of antipsychotics and mood-​
stabilizing medication to treat impulsivity and aggression in people
with borderline personality disorder. There is less evidence for the use
of antidepressant medication, but comorbid mental disorders such
as anxiety and depression may respond well to pharmacotherapy.
Admission to a psychiatric hospital ward is rarely helpful as it may
exacerbate rather than reduce problem behaviours and may lead to
problematic interactions with other patients. This is therefore usu-
ally reserved for those cases where risk to self or others cannot be
satisfactorily managed in the community.
The successful management of personality disorder in the medical
setting requires the recognition of the problem and a clear and con-
sistent plan for how to respond to the patient’s behaviour. A written
care plan can be helpful. It is important that all clinicians involved
in the patient’s care understand that the person has a diagnosis of
personality disorder and what specific problems that poses both for
the patient and those caring for them. It is important for staff to rec-
ognize what difficulties arise in interactions with the patient, to be
aware of these, and to avoid being drawn into behaving in a dismis-
sive, punitive, or overly caring way.
Outcome
By definition, personality disorders tend to persist. Patients with
personality disorders with traits such as sensitivity to rejection
and impulsive behaviour are at increased risk of suicide and other
causes of premature mortality. However, many of the problematic
behaviours associated with some types of personality disorder, such
as self-​harm, excessive use of healthcare services, aggression, and
offending behaviours, tend to improve over time.
FURTHER READING
Goves, JE (1978). Taking care of the hateful patient. N Engl J Med,
298, 883–​7.
Stoffers JM, et al. (2012). Psychological therapies for people with bor-
derline personality disorder (Review). Cochrane Database Syst Rev,
8. CD005652.
Tyrer P, Reed GM, Crawford MJ (2015). Classification, assessment,
prevalence, and effect of personality disorder. Lancet, 385, 717–​26.
Box 26.5.13.3  Dialectical behaviour therapy for the treatment
of borderline personality disorder
Dialectics is a philosophical term which describes the process of re-
solving seemingly contradictory positions.
Core dialectic of dialetical behavioural therapy:
The individual learns to accept the way they are, while at the same time,
striving to make positive changes in their life.
Structure of dialetical behavioural therapy
Individual therapy addresses the core treatment goals:
•	 Reduction of self-​harming behaviour
•	 Reduction of behaviours that interfere with therapy
•	 Improvement of quality of life
Group-​based skills training:
•	 Distress tolerance aims to improve the person’s ability to tolerate
and manage extreme distress.
•	 Interpersonal effectiveness aims to teach skills which allow im-
proved interpersonal relationships.
•	 Emotion regulation aims to improve the ability to control disturb-
ances in mood and other distressing emotions.
•	 Mindfulness is a set of skills whose aim is to cultivate greater
awareness of the current state of the mind and body, instead of
becoming preoccupied with worries and falling into a spiral of
distressing emotion.
Individuals may also telephone their therapist during crises to learn
how to use skills in real-​life situations.
Therapists meet weekly for group supervision with other practitioners
of dialetical behavioural therapy where issues relating to therapy can
be discussed.

26.5.2 Dementia 6478 Bart Sheehan
26.5.2 Dementia 6478 Bart Sheehan
SECTION 26  Psychiatric and drug-related disorders
6478
26.5.2  Dementia
Bart Sheehan
ESSENTIALS
Dementia is a clinical syndrome, not a specific disease. It is character-
ized by impairment of mental functions leading to memory loss, be-
havioural changes, and impairment in the activities of daily living. It
may be caused by several different diseases, the most common being
Alzheimer’s disease, vascular dementia, and Lewy body dementia.
There are other potentially treatable causes, including depression,
which must be excluded.
Drug treatment with cholinesterase inhibitors may reduce the
progression of dementia for a period, especially in Alzheimer’s dis-
ease. Antipsychotic drugs should be used with great care. The asso-
ciated impairment and behavioural problems often requires social
care, sometimes in institutions, and will place an increasing burden
on medical services and society.
Introduction
Dementia is a clinical syndrome in which brain disease leads to ac-
quired global impairment of higher mental functions despite clear
consciousness. It can be thought of as chronic ‘brain failure’. It is
usually (but not always) progressive and usually (but not always)
found among older people. The functions affected include cognitive
function, particularly amnesia (memory loss), dyspraxia (difficulty
carrying out complex motor actions), dysphasia (difficulty with
speech), and agnosia (inability to recognize and interpret sensory
inputs). There may also be psychiatric and behavioural symptoms,
in descending order of frequency: depression, paranoid ideas, mis-
identifications, hallucinations, aggression, and wandering. Finally
there are deficits in activities of daily living (ADLs), with progres-
sive impairment in ability to manage both instrumental ADLs (e.g.
cooking, using telephone, managing bills) and basic ADLs (washing/​
dressing/​elimination).
Aetiology
Dementia is caused by many different diseases. Alzheimer’s disease
is responsible for about half of cases, and in post-​mortem series the
other common causes are vascular dementia (20–​30% of cases), de-
mentia with Lewy bodies (10% of cases), and frontotemporal de-
mentia (2–​5% of cases). Table 26.5.2.1 shows likely causes, grouped
by neuropathological mechanisms.
Epidemiology
The prevalence of dementia is similar in most countries and most races.
Men and women are about equally affected. The incidence in younger
and middle-​aged people is low and increases with age. Five to seven per
cent of people aged 65 and over are affected, and 40% of people aged 95
and over. Worldwide this means that in 2014 about 45 million people
had dementia, a figure that is projected to triple by 2050. Already, over
half of people with dementia are in low-​ and middle-​income countries,
which will also see the greatest rises in coming decades.
Clinical features
General
The clinical features vary according to the cause. Distinguishing be-
tween causes may be difficult clinically, especially in the early stages
of disease. Patients with dementia usually have histories of acquired
progressive memory loss (e.g. forgetting to take tablets or repeating
things), with associated deficits in other cognitive areas, especially
speech (expressive or receptive dysphasia), dyspraxia (e.g. difficulty
carrying out complex motor sequences like cooking or dressing),
and agnosia (e.g. not recognizing oneself in the mirror). There is
frequently difficulty in coping with the basic activities of daily living;
for example, relatives may have to take over managing finances or
shopping, or the patient may become repeatedly lost in a previously
familiar place. The patient or relative may also describe failure to
cope with a situation they would previously have easily mastered, for
example, a holiday abroad.
As the dementia progresses, the patient shows worsening failure
in multiple areas of life, with increasing dependency on others to
accomplish even the basic activities of daily living. Other changes in
behaviour such as apathy or irritability are commonly noted at some
point of the illness, as well as behavioural changes like wandering,
insomnia, and aggression.
Alzheimer’s disease (AD)
Alzheimer’s disease, the commonest cause of dementia, is a
neurodegenerative condition in which there is progressive loss of
cortical tissue associated with two hallmark neuropathological
findings; extracellular accumulation of amyloid in plaque-​like for-
mations, and intracellular neurofibrillary tangles:  paired helical
fragments of hyper-​phosphorylated Tau (a microtubule-​associated
protein). These pathological findings are the only absolute diag-
nostic criteria for diagnosis of AD. To date, aetiological theories have
centred on the likelihood that a primary malfunction in metabolism
of amyloid is central to AD, though lack of therapeutic progress has
led to questioning of this hypothesis. Progression is often relentless,
Table 26.5.2.1  Causes of dementia
Neurodegenerative causes
Alzheimer’s disease
Vascular dementia
Dementia with Lewy bodies
Frontotemporal dementias
Dementia in Parkinson’s disease
Hydrocephalus
Infective causes
Dementia in HIV
Syphilis
Creutzfeld–​Jacob disease
Intoxications and metabolic causes
Alcoholic dementia
Heavy metal poisoning
Vitamin deficiencies, especially B12
Miscellaneous causes
Head injury
Anoxic brain injury
26.5.2  Dementia
6479
with a typical history of 2–​3 years of symptoms at diagnosis, and
progression to death after 7–​10 years of illness.
Vascular dementia
In vascular dementia, the accumulation of cortical and subcortical
areas of neuronal loss due to infarction (and sometimes haem-
orrhage) leads to escalating cognitive and behavioural change.
Infarction is much more common than haemorrhage, though per-
haps 10% of patients show micro-​haemorrhages on MRI, which
suggest cerebral amyloid angiopathy. Up to 20% of community pa-
tients with dementia are eventually diagnosed with mixed dementia
(due to evidence of both Alzheimer’s disease and vascular path-
ology). Onset may be sudden and associated with clinical evidence
of stroke. Progression is typically stepwise, indicating recurrent and
accumulative cerebrovascular events. Patients may retain insight if
cortical damage is not widespread. A history of stroke, hypertension,
and neuroimaging evidence of cerebrovascular disease support this
diagnosis. Prognosis is likely to depend on the wider cardiovascular
risk status of the patient, but progression to death over 5–​7 years, as
in AD, is typical.
Dementia with Lewy bodies
This clinical syndrome is of dementia characterized by severe fluctu-
ation (often over hours), evidence of Parkinsonism, and the presence
of striking visual hallucinations. Supportive features include the pres-
ence of sleep/​wake cycle disruption, sensitivity to neuroleptics (often
prescribed due to hallucinations), and deficient dopamine transporter
uptake in the basal ganglia on SPET or PET imaging. The clinical syn-
drome can therefore be clearly identified with high precision in life.
The hallmark of this condition is the deposition of an intracellular
body called a Lewy body, which consists primarily of ubiquitin and α-​
synuclein. The clinical course is not clearly different to that of AD.
Frontotemporal dementia
These are a group of dementias, among which the best known is
Pick’s disease. A family history may be prominent, with earlier age
of onset (50s/​60s) than with other dementias. There may be striking
personality change early in the condition, with coarsening, emo-
tional lability, and disinhibition. These changes are essentially the
frontal variant of frontotemporal dementia. Dysphasia may also be
prominent early, often with loss of recognition for words and dif-
ficulties with expressive speech. This is essentially the temporal
variant of frontotemporal dementia. CT/​MRI imaging may show
marked frontotemporal atrophy, while functional neuroimaging is
likely to show significant frontotemporal hypoactivity. Conditions
in which there is abnormal expression of the microtubule-​associated
protein Tau (known as Tauopathies) are now recognized as leading
to the clinical features of frontotemporal dementia.
Differential diagnosis
Delirium
Delirium shares with dementia the finding of cognitive impairment
and often significant behaviour problems. Unlike dementia, the
onset of delirium is usually rapid, usually transient, and the clin-
ical features include inattention, impairment of consciousness, and
marked fluctuation during its clinical course.
Depression
Patients with depression are frequently apathetic with social with-
drawal, poor concentration, and retardation leading to poor perform-
ance on formal cognitive tests. This sometimes leads to misdiagnosis of
depression as dementia; so-​called depressive pseudo-​dementia.
Mild cognitive impairment
This term is used for people at high risk of dementia who have cog-
nitive deficits (usually defined as a memory performance at least
1.5 standard deviations below expected norms for age and popula-
tion) with associated functional impairment, but no clear dementia.
It conveys a 10–​15% risk of incident dementia each year (about 10
times higher than that of age-​matched peers).
Clinical investigations
History taking is the most important investigation in diagnosing
dementia, and must involve a collateral history from someone who
knows the patient well. Tests of cognitive functioning can help screen
for dementia, increase the precision of diagnostic decisions, and also
help to objectively monitor change over time. Blood tests are useful
in excluding rare causes of dementia. Neuroimaging is now a routine
part of the investigation of dementia.
Cognitive tests
Many structured cognitive tests are available for use with patients
suspected of having dementia. The most commonly used in the last
three decades has been the Mini-​Mental State Examination (MMSE).
Like other common tests, it covers several cognitive areas (memory,
recall, orientation, concentration, praxis, receptive and expres-
sive speech, and visuo-​motor ability) and is short (10–​15 minutes
for most patients). It is reasonably effective as a screening tool and
can crudely monitor progress (e.g. after initiation of drug therapy).
False positives (e.g. due to delirium, depression, tiredness, sedation,
learning disability, sensory impairment) are, however, common.
More detailed cognitive tests can significantly improve the preci-
sion of diagnosis and are especially important in early or borderline
cases. Administering them often requires specialist resources.
Blood tests
Routine assessment of suspected dementia should include the fol-
lowing tests: thyroid function, full blood count, urea, and electro-
lytes, liver function tests, blood sugar, B12/​folate. Syphilis serology
and HIV testing are recommended in some clinical populations, but
may have low yield in routine memory clinic practice.
Neuroimaging
CT and MRI scanning provide structural images of the brain. Both
will identify mass lesions and help to exclude those causes of de-
mentia likely to be amenable to surgical intervention (e.g. normal
pressure hydrocephalus, subdural haematoma; see Fig.  26.5.2.1).
Shrinkage of medial temporal lobe structures and of the hippo-
campus may be observed in early AD.
Functional imaging may help to identify frontotemporal deficits
in frontotemporal dementia (FTD; see Fig. 26.5.2.2). In dementia
with Lewy bodies, deficient dopamine basal ganglia uptake on
single-​photon emission computed tomography (SPET) or PET
SECTION 26  Psychiatric and drug-related disorders
6480
imaging strongly supports the diagnosis. In recent years, amyloid
ligand imaging on PET scanning has raised the possibility of the
very early detection of AD, even before the clinical syndrome can
be detected, but the high rate of false positives means that this test
cannot be recommended in routine practice.
Treatment
Drug therapy
The treatment of dementia depends on the underlying cause. Great
effort has been directed at finding effective biological treatments for
the common causes of dementia. In AD, cholinergic neuronal loss
is extensive from the early stages, hence the use of cholinesterase
inhibitors which prevent the breakdown of the neurotransmitter
acetylcholine is rational. These are the current mainstay of AD treat-
ment, with available drugs shown in Table 26.5.2.2.
Cholinesterase inhibitors have clear benefit in AD, delaying pro-
gression of the disease for one to two years on average, rather than
reversing established deficits. Withdrawal of these agents is then as-
sociated with a worsened prognosis long term, hence they should be
continued as long as side effects allow. While most patients tolerate
them well, cholinergic side effects, especially gastrointestinal prob-
lems and in some patients brady-​arrhythmias, can be problematic.
Cholinesterase inhibitors are sometimes also used in vascular de-
mentia, though the risk/​benefit balance in the condition is unproven.
(a)
(b)
(c)
(d)
Fig. 26.5.2.1  Hydrocephalus. (a) and (b): Two preoperative computed
tomography (CT) scans in an elderly adult who presented with
cognitive decline and other neurological features. (c) and (d): Following
ventriculoperitoneal shunting (arrow in d), the communicating
hydrocephalus resolved with complete recovery of the patient.
Reproduced from Ian Whittle. Raised intracranial pressure, cerebral oedema, and
hydrocephalus, from Dementia: Comprehensive Principles and Practices by
permission of Oxford University Press.
RH
(a)
(b)
LH
RH - Lateral
Fig. 26.5.2.2  (a) Magnetic resonance imaging (MRI) demonstrating bilateral (right [RH]
greater than left [LH]) frontal, temporal, and parietal atrophy. (b) Fludeoxyglucose positron
emission tomography (FDG-​PET) showing prominent bilateral (right greater than left)
frontal and temporal hypometabolism (indicated by blue colour).
Reproduced from Bradford C. Dickerson, Frontotemporal Dementia, from Dementia: Comprehensive
Principles and Practices by permission of Oxford University Press.
26.5.2  Dementia
6481
In Lewy body dementia, trials of these agents have shown promise
and they are usually recommended.
More recent efforts to treat AD have focused on active, and lat-
terly passive, vaccination strategies designed to elicit an immune re-
sponse to amyloid in the earliest states of disease, but thus far these
have not proven effective.
Social care
Despite progress with drug therapy the mainstay of treatment for
dementia remains social; family members still provide the vast ma-
jority of care for people with dementia. Up to half of people with
dementia in Western countries will eventually spend some period of
time in institutional care, though most remain outside such settings.
The associated costs of care are clearly enormous and increasing.
From the societal perspective, the greatest costs accumulate in the
later stages of illness, in particular due to hospitalization and the
costs of nursing home care, though the direct healthcare costs are
always outweighed by those of social care. At all stages, the greatest
costs are probably the indirect costs borne by family carers.
Treating the psychological and behavioural problems
of dementia
Most patients with dementia will develop some behavioural or
psychological symptoms during the course of their illness. These
include low mood, obsessionality, or psychotic symptoms, and
behavioural problems like apathy, agitation, insomnia, aggression,
and wandering. These symptoms are unsurprisingly the strongest
predictors of carer strain and institutionalization of the patient.
Many are dealt with simply by the patience and skill of family or
paid carers. In some cases medication is requested, but few medi-
cations have high-​quality controlled trial evidence to support their
use for this purpose. Risperidone has been shown to improve ag-
gression in patients with AD and is licensed for this indication in the
United Kingdom. All other prescribing is off licence. Medications
with a high risk of worsening cognitive impairment, sedation, and
falls (e.g. benzodiazepines) are still often used. Antipsychotics
are known to increase risk of stroke and mortality in dementia
and should only be used for short periods after evaluation of risk/​
benefit.
Future developments: Can dementia
be prevented?
In the absence of an effective treatment for most causes of de-
mentia, and the vast socioeconomic costs, preventive strategies
have been widely promoted. Dementia is especially difficult to
prevent as the earliest pathological changes in the disease may
occur decades before the clinical features become obvious. Delays
of even six months in the onset of clinical symptoms would re-
duce the population prevalence appreciably (5–​10%), while a
delay of five years could reduce the population prevalence by up
to 50%. Recent epidemiological evidence raises the possibility
that the prevalence of dementia in Western countries may be al-
ready falling, possibly due to lifestyle changes aimed at improving
cardiovascular health. Risk factors that may contribute to risk of
dementia and which may be amenable to intervention are listed
in Table 26.5.2.3.
FURTHER READING
Folstein MF, Folstein SE, McHugh PR (1975). ‘Mini-​mental state’: a
practical method for grading the cognitive state of patients for the
clinician. J Psychiatr Res, 12, 189–​98.
Kales HC, Gitilin LN, Lyketos CG (2015). Assessment and manage-
ment of behavioral and psychological symptoms of dementia. BMJ,
350, h369.
Rabins PV, Blass DM (2014). In the clinic: dementia. Ann Intern Med,
161, ITC1; quiz ITC16.
Robinson L, Tang E, Taylor JP (2015). Dementia: timely diagnosis and
early intervention. BMJ, 350, h3029.
Table 26.5.2.2  Antidementia drug treatments (licensed in United Kingdom, July 2018)
Drug class
Starting dose
Target dose
Common side effects
Cholinesterase
inhibitors
Donepezil
5 mg OD
10 mg OD
Nausea, diarrhoea, frequency, dizziness, psychiatric effects
Rivastigmine
1.5 mg BD
3–​6 mg BD
Galantamine
8 mg /​24 hours
24 mg/​24 hours
Glutamate antagonist
Memantine
5 mg OD
20 mg OD
Constipation, headache
Table 26.5.2.3  Potential mediators of dementia risk (known risk
factors)
Evidence is
Risk factor
Notes
Supportive
Intelligence
No feasible intervention
Hypertension
Treatable
Depression
Treatable
Diabetes
Treatable
Contradictory
Exercise
Inactivity increases risk
Obesity
Recent evidence suggests low weight
increases risk
Diet
Mediterranean diet most commonly
recommended
Vitamins
B vitamins, E vitamins show promise
in early research
Not supportive
Mental activity
Best evidence suggests brain training
interventions ineffective
Social
engagement
Social benefits unlikely to be
accompanied by lower dementia risk

26.5.3 Organic psychoses 6482 Curtis McKnight and
26.5.3 Organic psychoses 6482 Curtis McKnight and Jason Caplan
SECTION 26  Psychiatric and drug-related disorders
6482
26.5.3  Organic psychoses
Curtis McKnight and Jason Caplan
ESSENTIALS
A psychosis is a syndrome characterized by delusions and hallu-
cinations. Organic psychoses refer to those psychoses attributed to
identifiable brain diseases and are thereby distinguished from pri-
mary psychoses such as schizophrenia. Almost any condition that
affects the brain can cause an organic psychosis. Delirium and de-
mentia are the most common, although there are many other causes
including other neurodegenerative diseases, autoimmune disorders,
multiple sclerosis, endocrinopathies, metabolic disorders, and infec-
tions. Making the diagnosis of an organic psychosis requires a high
index of suspicion and appropriate investigation. The treatment is
usually that of the primary disease when that is possible, while the
symptoms of psychosis can be managed using antipsychotic drugs.
Introduction
The term ‘organic psychosis’ describes syndromes of psychotic symp-
toms directly attributed to an identifiable pathophysiological cause.
Differentiation of these disorders and the ‘primary’ or ‘functional’
psychoses (which includes schizophrenia and psychotic symptoms
due to mood disorders) presumes that these latter diagnoses are not
‘organic’ in nature. However, as we gain a greater understanding of
the anatomic and physiologic substrate of so-​called mental illness, it
is likely that the term ‘organic psychosis’ will become less meaningful
and have to be replaced by another such as ‘secondary psychosis’.
Neurodegenerative diseases
Dementia
In DSM-​5, the dementias are subsumed under the designation of
major neurocognitive disorder (MND), though the term dementia
will likely remain in widespread use and have a role in the names
of various existing subtypes. These disorders include a multitude of
pathologies (Box 26.5.3.1), with Alzheimer’s disease being the most
common.
Anyone presenting with new onset psychosis late in life must be
considered as having organic psychosis for a length of time until
or unless a classic syndromal MND reveals itself. In some cases,
high premorbid cognitive functioning and a large cognitive re-
serve along with asymmetric brain pathology make dementia dif-
ficult to identify in a patient presenting with psychosis. Psychosis
due to a dementia presenting after age 65 is most likely to be due to
Alzheimer’s disease simply because this is the most common form
of dementia in this age group. For patients younger than 65 years of
age, frontotemporal dementia (FTD) is as common as Alzheimer’s
disease. FTD is a collection of pathologies that are clinically divis-
ible into three types: behavioural variant frontotemporal dementia
(bvFTD), semantic variant of primary progressive aphasia, and non-​
fluent variant primary progressive aphasia, although the autopsy
histopathologies for these three subtypes do not correlate well with
their phenotypes. The most common of these is bvFTD. By some es-
timates, 50% of patients with bvFTD are initially misdiagnosed with
a primary psychiatric illness.
Parkinson’s disease
Parkinson’s disease is characterized by a resting tremor, rigidity and
bradykinesia related to formation of Lewy bodies with resulting
destruction of dopaminergic neurons in the substantia nigra.
Current treatment is directed at improving dopamine transmission
and function in the remaining neurons. Dementia is common in
Parkinson’s disease although typically presents later in the course.
Early psychotic symptoms in Parkinson’s disease (absent dopamine
medications and prior to MND) are unusual and may cast doubt
on the veracity of the diagnosis. Often psychotic symptoms in
Parkinson’s disease are comorbid with depression or visual acuity
changes, so psychotic depression or Charles Bonnet syndrome can
be included in the differential. Finally, the current mainstay of treat-
ment for Parkinson’s disease includes dopamine enhancers, which
have a well-​known proclivity for causing psychosis. As such, evalu-
ation and (if possible) reduction of these medications is a recom-
mended first step in treatment. If dopamine medication reduction
is not possible, pimavanserin, a newly developed specific agent for
the treatment of psychosis in Parkinson’s disease that functions as a
selective serotonin inverse agonist, may have benefit. If these meas-
ures prove unsuccessful, cautious attempts to treat psychosis with
low doses of neuroleptics that have low affinity for the D2 receptor
(i.e. clozapine) may be undertaken.
Epilepsy
Psychosis can be an ictal, post-​ictal, and interictal phenomenon in
patients with seizure disorders. As an ictal manifestation, psychosis
has been most reported in complex partial seizures (since a general-
ized seizure would mask any ictal psychosis), usually of the temporal
lobe (with only approximately 30% of these patients presenting with
seizure focus outside of this region). As one might expect of an ictal
presentation, psychotic symptoms in these cases are limited to the
duration of the seizure itself.
Postictal psychosis occurs in 10% of patients undergoing video-​
EEG monitoring. A window ranging from hours to days between
the cessation of seizure activity and the onset of psychotic symptoms
is described. The mean duration of post-​ictal psychoses is about 70
hours, and the extinction of these symptoms is accelerated by use of
relatively low dose neuroleptic medication.
Box 26.5.3.1  Subtypes of major neurocognitive disorder
Alzheimer’s disease
Vascular disease
Frontotemporal lobar degeneration
Lewy body disease
Traumatic brain injury
Substance/​medication use
HIV infection
Prion disease
Parkinson disease
Huntington disease
Due to another medical condition (e.g. multiple sclerosis)
Combined or multiple aetiologies
26.5.3  Organic psychoses
6483
One analysis of the available evidence estimates a 6–​12 times
greater likelihood of psychosis in people with epilepsy than in the
general population. Paranoia and hallucinations are especially
prominent findings in chronic interictal psychosis. The average age
of onset of chronic psychotic symptoms in patients with epilepsy
(30 years) is later than in those without epilepsy.
Autoimmune disorders
The common factor in autoimmune disorders is a misdirected im-
mune response that results in damage to endogenous tissue. When
the targeted tissue lies with the central nervous system, clinical pres-
entation is likely to include neuropsychiatric symptoms, and when
that tissue lies within the limbic circuit, clinical presentation is likely
to include symptoms of psychosis (Table 26.5.3.1).
Autoimmune encephalitis
Autoimmune encephalitis is a group of disorders that present with
neurological and psychiatric presentations prompted by antibodies
directed against a broad group of neural proteins. Initially referred
to as paraneoplastic limbic encephalitis (since it was believed that
the presence of cancer proteins prompted production of the culpable
antibodies which subsequently cross-​reacted with nervous system
targets), the name was shortened to limbic encephalitis when a series
of cases were described in the absence of any cancer. The name was
later updated to autoimmune encephalitis in light of several cases
in which the neural injury occurred outside of the limbic circuit.
Nonetheless, a previously undetected cancer remains a concern in
newly diagnosed cases of autoimmune encephalitis.
Autoantibodies implicated in autoimmune encephalitis can be
broadly divided into two types: those directed against cell mem-
brane targets and those directed against intracellular targets (Table
26.5.3.2). Of these two groups, antibodies directed against cell mem-
brane targets have been most frequently associated with psychosis
while the intracellular group more typically present with cognitive
decline, lethargy, and disorientation.
While the paraneoplastic association is no longer a diagnostic ne-
cessity, cancer remains the most frequent underlying cause. Thus, the
profile of individuals most at risk for these disorders mirrors those at
risk for cancer. Some antibodies have been associated with specific
malignancies (Table 26.5.3.3). Of particular diagnostic significance
are cancers that typically present in younger individuals, since these
presentations may be more easily mistaken for ‘first break’ schizo-
phrenia because they manifest in the second or third decade of life. The
clinical presentation of a young man with lethargy and confusion in
the presence of anti-​Ma2 antibodies raises the possibility of testicular
cancer. Similarly, a young woman presenting with symptoms of psych-
osis and anxiety in the presence of anti-​NMDA-​receptor antibodies
suggests ovarian teratoma. Definitive diagnosis requires specific testing
of serum and cerebrospinal fluid (CSF) for these autoantibodies since
neuroimaging and routine CSF studies can be non​specific. The EEG
may be abnormal with a characteristic pattern described as ‘extreme
delta brush’ with baseline rhythmic δ-activity at 1–​3 Hz with rapid
β-activity of 20–​30 Hz superimposed on the crest of each δ-wave. The
finding is relatively specific to the anti-NMDA-receptor antibody sub-
type of autoimmune receptor encephalitis.
Treatment of autoimmune encephalitis requires the identification
and removal of any inciting lesion (i.e. a cancer) and modulation
of the immune system. If an autoimmune encephalitis is suspected,
Table 26.5.3.1  Some of the major neural structures of the limbic
circuit
Cortex
Orbitofrontal cortex
Piriform cortex
Limbic lobe
Hippocampus
Entorhinal cortex
Fornix
Subcortex
Amygdalae
Nucleus accumbens
Septal nuclei
Diencephalon
Hypothalamus
Mammillary bodies
Anterior thalamic nuclei
Table 26.5.3.2  Autoantibodies implicated in autoimmune
encephalitis
Intracellular
Anti-​amphiphysin
Anti-​Hu
Anti-​Ma2
Anti-​CV2/​Anti-​CRMP5
Anti-​Ri
Anti-​Yo
Anti-​Tr
Cell membrane
Anti-​NMDA-​receptor
Anti-​VGKC
Anti-​LGI1
Anti-​CASPR2
Anti-​AMPA
Anti-​GABAB
Table 26.5.3.3  Cancer/​antibody associations in autoimmune
encephalitis
Anti-​amphiphysin
Small cell lung cancer (SCLC)
Breast cancer
Anti-​Hu
SCLC
Non-​small cell lung cancer
Colon adenocarcinoma
Prostate cancer
Rhabdosarcoma
Neuroblastoma
Thymoma
Anti-​Ma2
Testicular cancer
Non-​small cell lung cancer
Breast cancer
Anti-​CV2/​CRMP5
Thymoma
SCLC
Breast cancer
Anti-​Ri
SCLC
Ovarian teratoma
Breast cancer
Endobronchial carcinoid
Anti-​NMDA-​receptor
Ovarian teratoma
Anti-​VGKC
Prostate cancer
Thymoma
Adapted from: Foster AR, Caplan JP. (2009). Paraneoplastic limbic encephalitis.
Psychosomatics, 50(2):108−113. Copyright © 2011, with permission from Elsevier.
SECTION 26  Psychiatric and drug-related disorders
6484
serum and CSF should be sent for antibody studies while the patient is
screened for any underlying neoplasm. If a cancer is found, it should
be treated aggressively as in some cases, excision of an underlying
cancer has proved curative. A variety of immunomodulation tech-
niques are recommended including administration of intravenous
steroids, plasmapheresis, and use of intravenous immunoglobulin.
If these approaches are unsuccessful, some have recommended pro-
ceeding to pulsed doses of cyclophosphamide or rituximab. There
is no evidence favouring one psychotropic agent over another in
managing specific manifestations of psychosis.
Steroid-​responsive encephalopathy associated
with thyroiditis (SREAT)
SREAT has replaced the previously favoured eponymous designa-
tion Hashimoto’s encephalopathy. First described by Lord Brain and
colleagues in 1966, the syndrome presents with a variety of symp-
toms, which include frank psychosis in 30% of patients. There are
thyroglobulin and/​or thyroperoxidase antibodies on testing. While
the first reported case was diagnosed with Hashimoto’s thyroiditis,
subsequent studies have not found an association between SREAT
and thyroid function (Box 26.5.3.2). The current leading hypothesis
is that the elevated thyroid antibodies serve as a marker of increased
autoimmunity and perhaps an as-​yet unidentified specific auto-
immune process. As the name suggests, the treatment for SREAT
is administration of corticosteroids, with plasmapheresis and intra-
venous immunoglobulin considered second-​line interventions.
Again, there is no good evidence favouring one psychotropic agent
over another in managing specific manifestations of psychosis.
Multiple sclerosis (MS)
Multiple sclerosis is a demyelinating disease that can present
with a variety of neurologic, somatic, and psychiatric symptoms
depending on the distribution of the demyelinating lesions. While
disturbances of mood are described, studies of the prevalence of
psychosis in MS vary from as few as 0% of patients to as many
as 17%. Studies, comparing MS patients with psychotic symptoms
to those without, have found increased lesion volume and greater
concentration of lesions in the periventricular white matter and
temporal regions. Immunomodulation to treat the MS is also ef-
fective for the psychosis, though adjunctive use of a neuroleptic
may also be beneficial.
Systemic lupus erythematosus (SLE)
The autoimmune manifestations of SLE affect several organ systems
including the kidneys, joints, skin, and central nervous system (CNS)
with estimates of 14–​75% of patients experiencing neurological and
psychiatric symptoms including psychosis; the majority have these
symptoms either before diagnosis or within the following year. More
than 100 specific autoantibodies have been reported in SLE and of
those, the anti-​RP antibody is the most extensively studied. While
anti-​RP testing does not discriminate between patients with or
without psychotic symptoms, psychotic symptoms have been asso-
ciated with higher titres.
Endocrinopathies
Thyroid
Thyroid hormones have well-​known roles in the regulation of
mood, cognition, and behaviour. Thyroid hormone receptors (T3
triiodothyronine type) are highly concentrated in the limbic system.
Thyroid hormones also modulate translation and action of sero-
tonin, dopamine, and other neurotransmitters. Nonetheless, isolated
psychosis is a rare presentation thyroid disease. In most cases there
will be clinical evidence of thyroid deficiency or excess (fatigue, cold
intolerance, weight gain in the former; heat intolerance, excessive
sweating, weight loss, palpitations, and gastrointestinal upset in the
latter). Useful investigations include thyroid-​stimulating hormone,
free thyroxine level, free triiodothyronine, and levels of thyroid car-
rier proteins. Treatment involves correction of the thyroid dysfunc-
tion while neuroleptics are used to manage the psychotic symptoms.
Steroids
Psychosis is a well-​known effect of exogenous corticosteroid admin-
istration. Disruption in the hypothalamic-​pituitary-​adrenal (HPA)
axis leading to elevated endogenous glucocorticoids (especially cor-
tisol) is equally likely to result in psychosis. Anabolic-​androgenic
steroids have a variety of adverse psychiatric effects, although psych-
osis as a single isolated presenting symptom is rare.
Noradrenergic
A pheochromocytoma is a catecholamine (mostly epinephrine) se-
creting tumour most commonly associated with anxiety. In some
cases, the agitation of severe anxiety can resemble psychosis. If
psychosis presents in this fashion, it is usually accompanied by par-
oxysmal tachycardia and hypertension.
Parathyroid
Though not specifically an endocrine disorder, Fahr syndrome (or
idiopathic basal ganglia calcification) is linked with derangements
of parathyroid hormone function (several other precipitating condi-
tions are also recognized). Calcification of the basal ganglia is readily
identifiable on neuroimaging. A host of other neurological and psy-
chiatric symptoms including movement disorders and cognitive de-
cline typically accompanies the symptoms of psychosis.
Metabolic disorders
The metabolic disorders are a diverse group of rare conditions that
may present with psychosis. Initially termed inborn errors of metab-
olism these are now more commonly referred to as congenital meta-
bolic diseases, inherited metabolic diseases, or hereditary metabolic
disorders. Most of these diseases are the result of single gene mu-
tations that lead to a single enzymatic deficiency or dysfunction.
There are hundreds of hereditary metabolic disorders and many re-
main poorly characterized. They can be grouped by the metabolic
process that is disrupted (Table 26.5.3.4) although many evade this
Box 26.5.3.2  Thyroid function in cases of SREAT
Hypothyroid c.20%
Euthyroid or subclinical hypothyroid c.70%
Hyperthyroid c.10%
26.5.3  Organic psychoses
6485
taxonomy. The chief clinical challenge is accurate and timely identi-
fication of these rare conditions in order to direct appropriate treat-
ment. Most cases of hereditary metabolic disorder are diagnosed in
childhood or early adulthood.
In a patient presenting with isolated first episode psychosis without
an abnormal physical examination or investigation it is unlikely that
the cause is an hereditary metabolic disorder. Atypical presentations
with abnormal physical and laboratory findings should, however, in-
crease suspicion of an hereditary metabolic disorder. A judicious ap-
proach in such cases is to investigate in proportion to the atypicality
of the psychosis (i.e. unusual variations in age and variety, chron-
icity, or severity of symptoms).
Many hereditary metabolic disorders can be treated, which usu-
ally requires closely coordinated referral and multidisciplinary care.
Often, when an individual with psychosis is subsequently found to
have a hereditary metabolic disorder, treatment of that condition
will result in improvement but not complete remission of psych-
osis. Of the hereditary metabolic disorders, urea cycle disorders,
remethylation disorders, and the porphyrias are generally the most
acute, identifiable, and treatable.
The urea cycle eliminates nitrogen by converting ammonia into
urea. Several enzymatic deficiencies can result in a urea cycle dis-
order. These may present at any age. The most common symptom
cluster featuring psychosis features hallucinations accompanied by
headaches and gastrointestinal symptoms. The treatment would in-
clude timely specialist referral and dietary interventions such as pro-
tein restriction. Valproic acid is contraindicated for these patients.
Remethylation disorders result from defective remethylation of
homocysteine to methionine resulting in increased serum homo-
cysteine levels and ineffective utilization of folate and vitamin B12.
This is usually due to genetic polymorphisms resulting in dysfunc-
tion of the enzyme methylenetetrahydrofolate reductase (MTHFR)
or deficiencies of cobalamin metabolism. Laboratory testing is avail-
able for the 40 or so polymorphisms identified in homocystinuria.
Remethylation disorders may present at any age and psychosis (dis-
organized behaviour, hallucinations) is generally accompanied by
elevated serum homocysteine. Other associated signs are throm-
bosis and neurologic deficits.
Acute intermittent porphyria is an autosomal dominant disease
with variable penetrance linked to deficiency of the porphobilinogen
deaminase enzyme. If psychosis presents in the context of this dis-
ease it is accompanied by recurrent unexplained pain, typically of
the abdomen. Avoidance of the inciting trigger (which may include
a broad variety of drugs) combined with carbohydrate infusion and
hematin or heme arginate (United States or the United Kingdom,
respectively) is the recommended course of treatment. Alcohol and
tobacco use are to be strictly avoided.
Wilson disease, Niemann-​Pick type C, and cerebrotendinous
xanthomatosis are more chronic in progression with psychosis typic-
ally presenting late. Wilson disease is an autosomal recessive disorder
caused by a mutation in the Wilson disease protein (ATP7B) gene
that causes pathologic copper accumulation in several organs, most
notably the liver and brain. Most diagnoses are made in preadolescent
children or young adults, although it may occur as late as the sev-
enth decade. Psychosis is found in only a small percentage of cases;
aggression or personality changes are more common. Unusually
early onset psychosis should precipitate testing for Wilson disease.
Since screening is relatively non​invasive and inexpensive, the clinical
threshold for proceeding with testing should be low.
Niemann-​Pick disease type C is a lysosomal storage disease re-
sulting from mutations in either the NPC1 or NPC2 gene. Psychotic
symptoms such as delusions and visual hallucinations may present
in isolation for many years prior to onset of neurologic deficits. Of
the hereditary metabolic disorders, this is most likely to be mis-
diagnosed as a psychiatric disorder because of its rarity (1:150 000
people) and lack of obvious motor deficits until late stages. When
present the commonest motor signs are ataxia, abnormal move-
ments, and vertical supranuclear gaze palsy. These findings can be
obscured by or misattributed to neuroleptic treatment. Testing is
available but currently expensive and requires laboratory culture of
the patient’s fibroblasts.
Cerebrotendinous xanthomatosis is due to mutations of the gene
GYP27A1. The enzyme deficiency from genetic mutation results
in build-​up of cholesterol in various tissues including the brain.
Individuals presenting with psychosis, ataxia, and juvenile cataracts
warrant further testing for this condition.
Infection
Theoretically, any infection of the central nervous system may
precipitate symptoms of psychosis depending on the structures
damaged. Moreover, any systemic infection can cause psychotic
symptoms in the setting of a delirium. Here we focus on infec-
tious agents that have been directly associated with psychosis (Box
26.5.3.3). Of these, neurosyphilis remains an important preventable
cause of psychosis. The rate of syphilis infection fell after the dis-
covery of penicillin, but since the early 1990s the rates of spirochete
Table 26.5.3.4  Hereditary metabolic disorders
Carbohydrate metabolism
Glycogen storage disease
Amino acid metabolism
Phenylketonuria, maple syrup urine disease,
glutaric acidemia type 1
Urea cycle
Carbamoyl phosphate synthetase
I deficiency
Organic acid metabolism
Alcaptonuria, 2-​hydroxyglutaric acidurias
Fatty acid oxidation and
mitochondrial metabolism
Medium-​chain acyl-​coenzyme
A dehydrogenase deficiency
Porphyrin metabolism
Acute intermittent porphyria
Purine or pyrimidine
metabolism
Lesch–​Nyhan syndrome
Steroid metabolism
Lipoid congenital adrenal hyperplasia,
congenital adrenal hyperplasia
Mitochondrial function
Oculocraniosomatic neuromuscular
disorder with ragged red fibres
Peroxisomal function
Cerebrohepatorenal syndrome
Lysosomal storage
Gaucher’s disease, Niemann-​Pick disease,
Tay-​Sachs disease
Dietary elements
Wilson’s disease
Methionine synthase,
remethylation
Elevated levels of homocysteine, folate or
B12 deficiency
Leukodystrophies
Cerebrotendineous xanthomatosis
Creatine deficiency
Guanidinoacetate methyltransferase
(GAMT) deficiency

26.5.4 Alcohol misuse 6486 Jonathan Wood
26.5.4 Alcohol misuse 6486 Jonathan Wood
SECTION 26  Psychiatric and drug-related disorders
6486
Treponema pallidum infection have been increasing. Given this re-
surgence, some recommend that patients with new onset psychosis
should be screened.
The human immunodeficiency virus (HIV) penetrates the central
nervous system, although the extent to which HIV disrupts neuronal
function and neurotransmission is unknown. As with other organic
psychoses, treatment of the underlying cause is paramount and in
this case preventative; antiretroviral therapy reduces the rate of new
onset psychosis in HIV infected persons. Organic psychosis from
HIV infection is more frequent in individuals with prior psychiatric
disorders, lower global cognitive performance, and brain atrophy,
suggesting it may be modulated through a dementia syndrome.
Other infectious agents causing encephalitis can present as or-
ganic psychosis. In these cases, early encephalitis may have mostly
non​focal findings and lumbar puncture with cerebrospinal fluid
analysis is required. Typically these conditions progress from initial
organic psychosis to a more clearly recognizable encephalitis picture
so early detection is important but difficult.
FURTHER READING
Clancy MJ, et al. (2014). The prevalence of psychosis in epilepsy: a sys-
tematic review and meta-​analysis. BMC Psychiatry, 14, 75.
Dalmau J, Rosenfeld MR (2014). Autoimmune encephalitis update.
Neuro Oncol, 16, 771–​8.
Demily C, Sedel F (2014). Psychiatric manifestations of treatable her-
editary metabolic disorders in adults. Ann Gen Psychiatry, 13, 27.
Fricchione GL, Carbone L, Bennett WI (1995). Psychotic disorder
caused by a general medical condition, with delusions: secondary
‘organic’ delusional syndromes. Psychiatr Clin North Am, 18, 363–​78.
Friedman JH (2013). Parkinson disease psychosis:  update. Behav
Neurol, 27, 469–​77.
Friedrich F, et al. (2014). Psychosis in neurosyphilis—​clinical aspects
and implications. Psychopathology, 47, 3–​9.
Lee SW, Donlon S, Caplan JP (2011). Steroid responsive enceph-
alopathy associated with autoimmune thyroiditis (SREAT) or
Hashimoto’s encephalopathy: a case and review. Psychosomatics, 52,
99–​108.
26.5.4  Alcohol misuse
Jonathan Wood
ESSENTIALS
Excessive intake of alcohol is common and increases the risk of
developing many medical conditions, as well as leading to psycho-
logical and social harm. Medical conditions commonly associated
with harmful use include upper gastrointestinal and liver disease,
hypertension, and accidents. The psychological state of alcohol de-
pendency makes it more difficult to reduce intake and physical de-
pendency may lead to a withdrawal syndrome after admission to
hospital. Withdrawal symptoms range from mild to severe and will
commonly require treatment to prevent complications of alcohol
withdrawal such as seizures. Delirium tremens is a life-​threatening
consequence of alcohol withdrawal that requires immediate active
management. The role of alcohol in the development of Wernicke–​
Korsakoff syndrome means patients will also need prophylaxis or
treatment for this in the acute medical setting.
Introduction
The use of fermentation to make alcohol out of sugars has been a
human activity for thousands of years. Drinking alcohol is cur-
rently seen as a normal part of Western society. The current World
Health Organization classification ICD-​10 divides abnormal alcohol
use into harmful use (F10.1) and alcohol dependence (F10.2). The
most recent American Psychiatric Association classification of psy-
chiatric disorders, DSM-​5, combines these into a single diagnosis
of Alcohol Use Disorder (AUD) with a spectrum of mild to severe.
Alcohol misuse is a significant cause of both psychiatric and medical
morbidity and mortality. As many as 20% of admissions to medical
wards in the United Kingdom are directly related to alcohol con-
sumption or to alcohol-​related illnesses.
Aetiology
Alcohol is an addictive drug, but not everyone who uses it develops
misuse. The aetiology of AUD includes genetic, psychological, and
social factors.
Genetic factors
The genetic transmission of misuse is polygenic, with many sus-
ceptibility loci, each with small or medium effects and low pene-
trance. There are also genes involved in the metabolism of alcohol
that are negatively associated with misuse. ALDH2 is an enzyme
that catabolizes acetaldehyde. People with less effective variants of
this enzyme have a transient accumulation of acetaldehyde when
alcohol is ingested which leads to aversive symptoms such as fa-
cial flushing and tachycardia, hence they are less likely to drink
excessively.
Box 26.5.3.3  Some infections associated with psychosis
Syphilis
Human immunodeficiency virus
West Nile Virus
Rabies
Lyme disease
Epstein–​Barr virus
Herpes encephalitis
Japanese encephalitis
St. Louis encephalitis
Eastern equine encephalitis
Subacute sclerosing panencephalitis
Brucellosis
Cryptococcus
Mycoplasma pneumoniae
Leptospirosis
Hepatitis B
26.5.4  Alcohol misuse
6487
Psychological factors
Alcohol ingestion is pleasurable for most people and therefore likely
to be repeated. Other psychological factors such as depression or
anxiety may play a role in the development of alcohol use disorders.
A particular association is with social anxiety as those who feel anx-
ious in social situations can ‘self-​medicate’ with the often readily
available alcohol.
Social factors
General social factors including the availability and price of alcohol,
as well as the acceptability of drinking are clearly important in
determining drinking behaviour. Individual factors such as adver-
sity, family interactions, and peer group influence may also favour
the development of alcohol misuse.
Epidemiology
In England, the 2007 Adult Psychiatric Morbidity Survey (APMS)
estimated the prevalence of hazardous drinking in adults aged over
16 as 24% (33% of men, 16% of women). This included 4% of adults
(6% of men, 2% of women) whose drinking could be categorized
as harmful. The level of excessive drinking in the United Kingdom
is higher than in most other countries of the world. Binge drinking
is generally more common in the young and less common in older
adults, but can often persist into middle age.
In 2012, 3.3 million (or 6%) of all global deaths were attributable
to alcohol misuse, making it the fifth leading risk factor for prema-
ture death and disability; among people between the ages of 15 and
49, it is the leading factor.
Alcohol harm and dependence
Harmful alcohol use is defined as a pattern of excess alcohol use that
damages the person’s physical or mental health.
Alcohol dependence is defined by meeting three of the following
criteria over the past year:
•	 cravings or compulsion to drink
•	 tolerance
•	 withdrawal symptoms
•	 difficulties controlling use
•	 neglect of alternative activities
•	 continuation of use despite harmful consequences
Alcohol problems commonly coexist with other mental illnesses and
social problems. A comprehensive assessment of the patient is there-
fore required, covering all the areas listed in Box 26.5.4.1.
Medical consequences of excess alcohol intake
Heavy use of alcohol leads to health-​related problems in most bodily
systems, with the risk of premature death increasing with intakes over
100g per week and substantially increasing at over 200g per week.
Liver
The liver is the primary site for alcohol metabolism and alcohol is
one of the most common causes of chronic liver disease. Excessive
alcohol use leads to a spectrum of changes, which range from fatty
liver to hepatic inflammation and necrosis (alcoholic hepatitis) to
progressive fibrosis (cirrhosis).
Only a relatively small number of heavy drinkers progress to liver
disease and so genetic and other factors must also play a role. The
association between alcoholic liver disease and the polymorphism
of genes encoding for alcohol metabolizing enzymes such as ADH,
ALDH2, and CYP2E1 is not clear.
Although men have higher rates of alcoholic liver disease, women
have a greater susceptibility to it.
Gastrointestinal
With regular, heavy alcohol use a variety of medical complications
involving the gastrointestinal tract and related organ systems can
develop. Associated oesophageal disorders include oesophagitis, oe-
sophageal varices related to liver disease, and oesophageal mucosal
tears. Other common upper gastrointestinal problems are gastritis,
duodenitis, and ulcer disease. Alcohol is also a common cause of pan-
creatitis and the incidence among heavy alcohol consumers is around
3% per year.
Cardiovascular
There is a well-​documented association between heavy alcohol
consumption and hypertension. There is an ongoing debate as to
whether moderate alcohol consumption has a beneficial effect on
blood pressure and cardiovascular risk. Heavy drinking is also a risk
factor for arrhythmias, cardiomyopathy, sudden cardiac death, and
stroke.
Musculoskeletal
High alcohol intake is associated with osteoporosis. This is likely
to be due to reduced bone formation during ongoing remodelling
and perhaps mediated by parathyroid hormone and calcium metab-
olism. Consuming more than two units of alcohol per day is a risk
factor for both osteoporotic and other fractures. In addition, alcohol
inhibits repair following a fracture, probably through suppression of
synthesis of an ossifiable matrix.
Alcohol can cause acute rhabdomyolysis (breakdown of muscle
tissue) following a period of more heavy use or in relation to with-
drawal. This typically advances over a few hours then recedes as the
Box 26.5.4.1  Areas covered in comprehensive assessment
Alcohol use, including:
–​	 consumption:  historical and recent patterns of drinking, and if
possible a collateral history from family member or friend
–​	 dependence symptoms
–​	 alcohol-​related problems
Other drug misuse
Physical health problems
Psychological and social problems
Cognitive functioning
Readiness and belief in ability to change drinking behaviour
SECTION 26  Psychiatric and drug-related disorders
6488
muscles heal. Chronic alcoholic myopathy generally affects prox-
imal muscles and may develop over years. Biopsy shows muscle at-
rophy affecting predominantly type II, especially type IIB, muscle
fibres. The myopathy recovers gradually with a reduced alcohol
intake.
Pulmonary
Alcohol use increases the risk of adult respiratory distress syndrome
(ARDS), probably via increasing alveolar epithelium permeability.
Alcohol also increases the rates and the morbidity and mortality
associated with community-​acquired pneumonia, particularly of
gram negative organisms.
Neurological
Alcohol can cause several neurological problems, including:
Delirium tremens
Delirium tremens may be the presenting picture of alcohol depend-
ence. This extreme reaction to withdrawal from alcohol typically oc-
curs 24–​48 hours after cessation. The delirium and is characterized
by acute confusion and agitation commonly coexisting with perse-
cutory delusions and hallucinations. It requires hospital treatment
and has a mortality of 1–​4%.
Withdrawal seizures
Seizures are a common complication of alcohol withdrawal. These
commonly occur 12–​48 hours after discontinuing alcohol but may
occur up to 10 days after stopping. They take the form of generalized
convulsions. Subsequent electroencephalograms (EEGs) after the
seizure and withdrawal period are normal.
Alcoholic dementia and cerebral degeneration
Cross-​sectional magnetic resonance imaging (MRI) studies have
shown smaller volumes of both grey and white matter in the cere-
bral cortex in those with a history of excessive alcohol use. The area
of greatest loss appears to be the frontal lobes.
Chronic heavy alcohol consumption is associated with several
neuropsychological deficits in abstract thinking, memory, learning,
attention, and psychomotor skills. These deficits can progress to a
dementia. The dementia associated with heavy alcohol use manifests
as deficits in executive functioning to short-​ and long-​term memory
problems, as well as behavioural abnormalities such as disinhibition,
apathy, or irritability.
Wernicke–​Korsakoff syndrome
Wernicke–​Korsakoff syndrome is caused by a deficiency of thia-
mine in the central nervous system. It has an abrupt onset with
an abnormal mental state, ophthalmoplegia (weakness of paralysis
of extraocular muscles), and truncal ataxia (ataxia affecting the
proximal musculature especially that involved in gait stability).
Untreated it may progress to a chronic syndrome with severe
anterograde amnesia, retrograde amnesia, and other cognitive
deficits.
Cerebellar degeneration
Damage to the cerebellum can contribute to deficits of gait and
balance in chronic heavy alcohol users. Commonly there is atrophy
in the anterior superior vermis.
Peripheral neuropathy
Alcoholic neuropathy is caused by a combination of the direct
toxic effects of alcohol and its metabolites on neurons and asso-
ciated nutritional deficiencies. Onset is usually slow and begins
with tingling or burning sensations in the peripheries. Later,
sensory loss or distal weakness may also appear which progress
proximally.
Endocrinological
Alcohol has widespread effects on the body’s hormonal systems.
Alcohol decreases testosterone secretion, which may lead to gynae-
comastia, impotence, and testicular atrophy. In women, even mod-
erate consumption can lead to significant reproductive problems by
increasing oestrogen, inhibiting follicle-​stimulating hormone, and
disrupting folliculogenesis. In addition, alcohol increases the re-
lease of prolactin in both sexes, which may contribute to some of the
aforementioned abnormalities.
Both acute and chronic alcohol use activates the hypothalamic-​
pituitary-​gonadal axis. In some drinkers a condition called alcohol-​
induced pseudo-​Cushing’s syndrome may develop. This is often
clinically indistinguishable from Cushing’s syndrome but present
more mildly. These symptoms will often disappear within a few
months of abstinence.
Both acute and chronic alcohol exposure to alcohol diminish
serum growth and insulin-​like growth factor-​1 levels in animals and
humans of both sexes.
Alcohol also has effects on the thyroid system with thyroid stimu-
lating hormone response blunted to thyrotropin releasing hor-
mone. Alcohol may lead to higher levels of parathyroid hormone
by decreasing gut absorption of calcium. Chronic heavy alcohol
use may increase insulin resistance in diabetics reflected in higher
haemoglobin A1C than matched patients.
Cancer
Heavy alcohol use increases the risk of oesophageal cancer around
tenfold. It is also associated with an increased risk of oral, pharyn-
geal, laryngeal, breast, bowel, and liver tumours.
Injuries
Alcohol is a cause of accidental injuries in both chronic heavy
drinkers and episodic drinkers. Alcohol-​impaired driving is esti-
mated to account for a third of all driving fatalities. There is a strong
link with accidents involving fires; two-​thirds of those who required
admission with burns were intoxicated at the time. Alcohol is also
implicated in drowning and falls, and is the biggest single cause of
accidents in the home.
Alcohol-​related complications of pregnancy
Although most women cease drinking excess alcohol in preg-
nancy, alcohol-​related birth problems are not uncommon. Birth
defects include reductions in weight, height, and head circum-
ference; decreased cognitive abilities and an increased risk of be-
havioural problems such as attention deficits and impulsiveness.
The so-​called fetal alcohol syndrome is characterized by growth
deficiency, facial dysmorphology, and central nervous system
(CNS) disorders. The current global estimated incidence is about
one in 1000 live births in the general obstetric population and
26.5.4  Alcohol misuse
6489
25 per 1000 births among alcohol-​dependent women. It is the
most common preventable cause of intellectual disability in the
Western world.
Clinical investigation
Investigations may indicate excess alcohol use by showing the ef-
fect the alcohol intake has had on the body. A blood count may
show macrocytosis, potentially with thrombocytopenia, due to
effects on the bone marrow. Liver enzymes, prothrombin time,
and bilirubin may all be raised, with a particular elevation in
γ-glutamyltransferase.
Treatment
Alcohol withdrawal
The most common situation where a general physician may come
across alcohol-​related problems is after admission to hospital. The
characteristic withdrawal symptoms related to alcohol can be both
unpleasant and medically dangerous; they are listed in Box 26.5.4.2.
Treatment of withdrawal is usually with benzodiazepines in a
fixed progressively reducing dose regimen (see Table 26.5.4.1).
Benzodiazepines ameliorate the imbalance between excitatory and
inhibitory neurotransmitter systems, treating unpleasant symp-
toms, and reducing the risk of complications such as seizure. The
doses used may need to be greater where there is severe dependence
and lower in patients whose benzodiazepine metabolism may be
suboptimal, such as older people and those with liver disease.
As an alternative to a fixed reducing regimen, a symptom-​
triggered regimen may be used; the drug is given according to the
symptoms. The revised Clinical Institute Withdrawal Assessment
for Alcohol (CIWA-​Ar) can be used to monitor withdrawal.
Carbamazepine is also used extensively in Europe to manage al-
cohol withdrawal and is an effective alternative to benzodiazepines.
A treatment regimen for outpatients might start at 800 mg in divided
doses on the first day, tapering to 200 mg on the fifth day.
Delirium tremens
The treatment of delirium tremens is with a high-​dose benzodi-
azepine; lorazepam or diazepam are commonly used. Treatment
with antipsychotic agents such as haloperidol or olanzapine may
also be required. Refractory delirium tremens treatment may neces-
sitate treatment with general anaesthetic agents, such as propofol,
with appropriate airway management.
Wernicke’s encephalopathy
Wernicke’s encephalopathy is best prevented by giving prophylactic
parenteral thiamine to all alcohol-​dependent patients admitted to
hospital. If Wernicke’s encephalopathy develops, high doses of par-
enteral thiamine should be given.
Psychological treatment of alcohol use disorders
Less than 10% of people with moderate to severe alcohol problems
receive treatment in a given year and only a third ever receive treat-
ment. The main treatment for alcohol problems is a talking therapy
which focuses on supporting the individual to change their behav-
iour and remain abstinent. The most commonly used intervention
for hazardous drinking that is given by physicians is brief simple
education and advice. For those with a special interest in alcohol
problems an extended brief intervention based on motivational
interviewing can be beneficial. The principles of motivational
interviewing are listed in Table 26.5.4.2.
For those with alcohol dependence, Alcoholics Anonymous (AA)
provides the most commonly available group-​based therapy. AA
is a fellowship for mutual support. The AA programme consists of
studying and following the ‘twelve steps’ which aim to help the al-
coholic to achieve a sober way of life. AA also advocates sponsor-
ship:  support from another AA member who offers one-​to-​one
guidance to those working through the programme.
Pharmacological treatment of alcohol dependence
Drugs are only used in combination with psychological treatment, and
few patients with alcohol use disorders receive pharmacotherapy, which
is intended to reduce the return to drinking in those who are abstinent.
Box 26.5.4.2  Symptoms of alcohol withdrawal
Autonomic hyperactivity (e.g. sweating, tachycardia, or anxiety)
Hand tremors
Headache
Insomnia
Nausea or vomiting
Short-​lived hallucinations or illusions
Psychomotor agitation
Grand mal seizures
Table 26.5.4.1  Sample alcohol withdrawal regimen for severe
dependence
Day
Dose of chlordiazepoxide
1
30 mg qds
2
25 mg qds
3
20 mg qds
4
15 mg qds
5
10 mg qds
6
10 mg tds
7
10 mg bd
8
5 mgs bd
9
5 mgs nocte
Table 26.5.4.2  Principles of motivational interviewing
Expressing empathy
Expressing empathy and acceptance helps build
rapport
Developing discrepancy
This helps the person to see that the addictive
behaviours do not fit with their longer-​term aims
and aspirations
Rolling with resistance
Avoiding getting into arguments, but offering
new perspectives helps prevent a breakdown in
communication
Supporting self-​belief
Supporting the person’s confidence that they can
make changes makes them seem possible

26.5.5 Substance misuse 6490 Stephen Potts
26.5.5 Substance misuse 6490 Stephen Potts
SECTION 26  Psychiatric and drug-related disorders
6490
Disulfiram (Antabuse) is a commonly used drug, but is only mod-
erately effective. It works by inhibiting aldehyde dehydrogenase,
which prevents the metabolism of acetaldehyde, alcohol’s main me-
tabolite. The build-​up of acetaldehyde leads to flushing, tachycardia,
nausea, vomiting, and sympathetic overactivity. This sympathetic
overactivity can also lead to acute hypertension and potential car-
diovascular or cerebrovascular harm. Patients must therefore be
counselled on the effects of drinking alcohol while on disulfiram, on
the need to avoid topical alcohol products, and about the potential
for hepatotoxicity. It is most effective when professionals or a sup-
portive partner or family supervises its use.
Acamprosate reduces short-​term and long-​term (more than
six months) relapse rates in patients with alcohol dependence
when combined with a talking treatment. It is thought to work by
modulating hyperactive glutamatergic N-​Methyl-​D-​aspartic acid
(NMDA) receptors. It is also only moderately effective.
Naltrexone is an opioid antagonist, which competitively binds to
opioid receptors and blocks the effects of endogenous opioids such
as β–​endorphin. It reduces cravings for alcohol and has a moderate
effect on the risk of a return to heavy drinking in the short term.
FURTHER READING
Day E, Copello A, Hull M (2015). Assessment and management of
alcohol use disorders. BMJ, 350, h715.
Mann K (2004). Pharmacotherapy of alcohol dependence. CNS Drugs,
18, 485–​504.
Room R, Babor T, Rehm J (2005). Alcohol and public health. Lancet,
365, 519–​30.
Wood A, et al. (2018). Risk thresholds for alcohol consumption: com-
bined analysis of individual-participant data for 599 912 current
drinkers in 83 prospective studies. Lancet, 391, 1513–23.
26.5.5  Substance misuse
Stephen Potts
ESSENTIALS
Many chemical substances are taken for their psychoactive proper-
ties, even if prescribed for other purposes. Such use and misuse of
psychoactive substances is so highly prevalent that it inevitably im-
pinges on medical practice. All physicians therefore need a general
understanding of the ways in which substance misuse may interrelate
with medical needs, as well as a specific understanding of the inter-​
relationships most relevant to their own area of medical practice.
Use of psychoactive substances may lead to acute intoxication
and its consequences, or the effects of chronic use and depend-
ence. Acute intoxication is associated with accidents and with acute
psychiatric and medical illness. Chronic misuse may cause medical
harm, which is often linked to the route of administration. Injection
of substances poses particular hazards. Drug dependence may lead
to great difficulties in the delivery of medical care. Clear policies and
communication with drug misuse services are an important part of
managing patients who are dependent on drugs such as opioids.
Introduction
When the recreational or dependent use of psychoactive sub-
stances inflicts harm, it becomes misuse. The incidence and preva-
lence of use varies by substance, setting, culture, and country, and
it changes over time. No area of medicine is unaffected by the phys-
ical and other harms caused by substance misuse. This chapter
aims to provide a framework to guide physicians, rather than pro-
viding a list of specific medical harms by substance. The illustrative
examples are drawn mainly from acute general medical inpatient
settings.
Substances that are misused
Table 26.5.5.1 provides a pragmatic classification of drugs of misuse.
Many of these agents and their effects are familiar to physicians.
The class ‘novel psychoactive substances’, also known as ‘clubbing
drugs’, includes many agents which have recently become easily
available in the United Kingdom and elsewhere (United Kingdom
law has made the alternative term ‘legal highs’ inaccurate). Drugs
that are usually prescribed can also be misused, such as opioid anal-
gesics or steroids for bodybuilding.
In ICD-​10, the physical problems caused by substance misuse are
divided into: (a) acute intoxication, (b) harmful use, and (c) depend-
ence. Physicians also see cases of acute poisoning, and of regular use
that is hazardous but not harmful. Medical services are increasingly
being encouraged to screen for hazardous substance misuse when
seeing patients for other reasons, and to offer advice or refer on as
appropriate. Table 26.5.5.2 lists harm from substance misuse and
Table 26.5.5.3 lists harms by drug type.
Acute poisoning and intoxication
Emergency departments and acute medical admission units are fa-
miliar with the presentation of acute opioid poisoning. This can
arise from deliberate overdose, or a recreational user’s misjudge-
ment of the potency of an unreliable illicit supply. Respiratory
depression, aspiration of stomach contents through an impaired
cough reflex, hypotension, and the consequences of prolonged im-
mobility can all arise, and may be fatal. The direct effect of the opioid
Table 26.5.5.1  Pragmatic classification of psychoactive substances
(other than alcohol and tobacco)
Group
Examples
Sedative/​hypnotics
Benzodiazepines, barbiturates
Opioids
Heroin, morphine, methadone, tramadol
Stimulants
Cocaine, amphetamine, methamphetamine
Hallucinogens/​
euphoriants
Cannabis, ecstasy, MDMA, LSD, ketamine
Novel psychoactive
substances (‘legal highs’,
‘club drugs’)
Multiple types, sold by brand name (e.g. ‘Ivory
Wave’)
Solvents
GHB, GBL, volatile solvents
Other
Anabolic steroids
26.5.5  Substance misuse
6491
is readily reversed by the antagonists naloxone or naltrexone, but
care must be taken to avoid subsequent deterioration if the drug
taken has a long half-​life and the dose was high. Aspiration pneu-
monia, rhabdomyolysis, compartment syndromes, and other con-
sequences need medical or surgical treatment in their own right.
Paradoxical excitation, where benzodiazepines cause disinhib-
ited behaviour, and thereby increase agitation, is less familiar. The
problem arises more often with recently prescribed administration
than with illicit use, especially when treating acute alcohol with-
drawal. If unrecognized, a vicious circle of escalating behavioural
disturbance and increasing doses can occur. Treatment involves
stopping all benzodiazepines and using instead antipsychotics such
as chlorpromazine or haloperidol.
Novel psychoactive substances can also cause serious acute
medical and psychiatric effects, which may be fatal. These include
rhabdomyolysis, acute kidney injury, seizures, hyperpyrexia, acute
psychotic states, and severe agitation. The sheer number of such
agents, uncertainty about what any given branded package actually
contains, and the absence of specific antidotes, means that man-
agement is symptomatic and pragmatic. Some of these agents have
a long half-​life and may therefore require treatment over a period
of days.
Harmful use
In chronic use, most psychoactive substances are less directly toxic
than alcohol. A  notable exception is the bladder damage associ-
ated with the euphoriant drug ketamine. Mucosal inflammation
and petechial haemorrhage cause symptoms of pain, frequency and
haematuria, and can progress to bladder fibrosis and renal failure.
Many harmful effects arise from the route of use, rather than
from the toxicity of the drug itself. Examples include perforation
of the nasal septum due to snorting cocaine, and the effects on the
airways of smoking cannabis. Repeated injection can lead to local
vascular problems through direct irritation (thromboembolism,
phlebitis); soft tissue problems through poor injection hygiene (cel-
lulitis, abscesses); and the familiar consequences of interpersonal
transmission of blood-​borne viruses (hepatitis C, HIV) or bacteria
(infectious endocarditis).
There are many psychiatric and neurological consequences of the
sustained use of psychoactive substances. Some solvents are directly
neurotoxic, with chronic use leading to cognitive deficits. Stimulants
can cause panic attacks, sustained anxiety, isolated psychotic symp-
toms (such as tactile hallucinations) and a paranoid psychosis re-
sembling schizophrenia. Cannabis too can cause a schizophreniform
psychosis with heavy use. Emerging evidence links it to the develop-
ment of schizophrenia itself, especially when use begins at an early
age and consequently acts on the developing brain. This relationship
appears to be dose-​related, so that the heavier and more prolonged
the use, and the more potent the cannabis consumed, the higher
Table 26.5.5.2  Types of medical harm arising from the use
of psychoactive substance
Type of harm
Subtype
Examples
Acute
Physical poisoning
Respiratory depression—​opioids,
benzodiazepines
stroke, MI—​cocaine
Intoxication
Oversedation—​opioids,
benzodiazepines
Paradoxical
excitation—​benzodiazepines
Psychotic symptoms—​novel
psychoactive substances,
hallucinogens, disturbed behaviour
Hazardous use
Regular use which has
not yet caused harm
but risks doing so
Harmful use
Direct toxicity
Bladder damage due to ketamine
Local consequences
of route of use
Nasal septum—​cocaine (inhaled)
Airways—​cannabis (smoked)
Thrombophlebitis
Abscesses—​anything injected
Cellulitis
Systemic
consequences of
route of use
Infective endocarditis, hepatitis C,
HIV—​anything injected
Mental/​behavioural/​
neurological effects
Anxiety—​stimulants
Psychosis—​stimulants, novel
psychoactive substances, cannabis
Depression—​stimulants
Cognitive deficits—​solvents
‘Flashbacks’—​hallucinogens
Dependence
see Table 26.5.5.3
Table 26.5.5.3  Severity and frequency of harm by drug type
Drug type
Acute effects
Chronic effects
Dependence
Physical
Psychiatric
Direct
Route-​
related
Psychiatric
Overall
Withdrawal risks
Sedative/​
Hypnotics
+
+
–​
+
_​
+++
+++
Opioids
+++
+
–​
+++
+
+++
++
Stimulants
++
++
+
++
+++
++
+
Hallucinogens/​
euphoriants
+
+++
+
+
++
–​
–​
Novel psychoactive
substances
+++
+++
?
++
+++
?
?
Solvents
++
+
+++
++
+++
+++
+++
Steroids
–​
–​
+++
–​
+++
–​
–​
+++, Major harm; ++, Moderate harm; +, Minor harm; -, Minimal/no harm; ?, Uncertain.
SECTION 26  Psychiatric and drug-related disorders
6492
the risk. Continued use after the development of psychosis or other
mental disorder also makes treatment more difficult.
Depression typically arises more from the non​medical (i.e. educa-
tional, social, financial, and legal) harms associated with sustained
substance misuse than from the drugs themselves, but depressive
symptoms are common in the ‘come-​down’ period after stimulant
use. Steroids have many psychiatric consequences, including de-
pression and psychotic episodes, which can be florid.
Dependence
Dependence on psychoactive substances constitutes a cluster of
physical, psychological, and behavioural characteristics associated
with sustained use. The key features seen in a medical context are
listed in Table 26.5.5.4, together with their main manifestations and
the implied roles for medical services.
Tolerance and loss of tolerance
This can be notable with opioids and sedative/​hypnotic drugs, such
as the benzodiazepines. Since these drugs are used as analgesics or
as sedation for medical and surgical procedures, a dependent user’s
tolerance can present problems in judging the correct doses, routes,
and frequency of administration when prescribing for medical use.
This is especially the case if the dependence is not recognized, or
the need to adjust doses insufficiently appreciated. ‘As required’
analgesia is not recommended in a dependent user and patient-​
controlled analgesia regimens need carefully set limits.
Loss of tolerance occurs after prolonged periods of abstinence
from a dependogenic substance such as an opioid while in hospital
(or prison). It confers risk, as a usually tolerated dose may become
fatally toxic. Patients should consequently be warned not to resume
consumption at previous levels on discharge.
Withdrawal syndromes
These can be problematic in medical settings. This is particularly
the case for opioids and benzodiazepines, although the severe with-
drawal associated with the anaesthetic agent γ-hydroxybutyrate is
becoming more common. Withdrawal from opioids causes sleepless-
ness, agitation, and autonomic effects (sweating, nausea, vomiting,
and diarrhoea). While intensely unpleasant, it carries a low mor-
tality. Withdrawal from benzodiazepines has physical and psycho-
logical manifestations similar to those of anxiety, but also brings a
risk of death from withdrawal seizures. This risk is higher when the
agent used has a short half-​life (such as lorazepam) or when there is
abrupt cessation of intake on entering a non​medical environment
(e.g. after arrest and imprisonment). γ-hydroxybutyrate withdrawal
is similar in nature to alcohol withdrawal, though often much more
severe in degree. It too carries a risk of withdrawal seizures.
Withdrawal states may present with medical manifestations such
as isolated seizures or a state resembling delirium tremens. The pri-
mary management aim is treatment via standardized dosage regi-
mens. These take two main forms: reducing fixed dose schedules, and
symptom-​triggered scales. In these regimens, long-​acting substitutes
such as diazepam and methadone are reduced in dose over a period of
days or occasionally weeks, together with agents to provide symptom
relief (e.g. loperamide for diarrhoea). Baclofen has recently been
found to be effective in managing γ-hydroxybutyrate withdrawal.
Withdrawal syndromes may also present incidentally, when pa-
tients admitted for unrelated medical or surgical problems have un-
recognized dependence. The main management aim here should
be prevention, by screening and taking proactive action for those
at risk. Early decisions may be required about substitute prescribing
and withdrawal regimens. These should be guided by a detailed his-
tory of the user’s normal daily and weekly levels of consumption,
as well as previous episodes of withdrawal. ‘As required’ prescrip-
tions should be minimized, and strict daily limits set on the total
doses of dependogenic prescribed drugs. These limits should be ex-
plicitly discussed with the patient. It is important that there is clear
communication across nursing shifts and ward transfers to ensure
the all-​important consistency of management. This is best ensured
via explicit, hospital-​wide protocols. Dependent users of illicitly ac-
quired drugs should be advised that the use of substitute prescribing
to treat or prevent withdrawal syndromes in medical settings is nor-
mally a temporary measure. It does not commit service providers to
continued prescription on discharge and referral to specialist drug
service should be offered instead.
Medically enforced withdrawal
Dependent users who have an established regimen of substitute drugs,
prescribed by drug treatment agencies, should generally have those pre-
scriptions respected. Medical teams treating seriously ill patients may
be tempted to impose opportunistic withdrawals from long-​established
prescriptions of opiates while the patient is ‘captive’. This is rarely wise,
as it often leads to destabilization on discharge, and a return to illicit use
with associated social disruption. Communication with drug misuse
prescribing services is therefore required in order to agree management
plans both during and after medical admission.
Rapid reinstatement after abstinence
This is a well-​established phenomenon, especially for opioids.
Patients who become abstinent during a medical admission, and
Table 26.5.5.4  Medically relevant features of dependence
on psychoactive substances
Feature
Manifestation
Medical role
Tolerance
Lack of response to normal
doses of analgesia and
sedation
Adjust doses
Withdrawal
syndrome
As cause of medical
admission
Treatment
Accompanying medical
admission
Prevention, screening,
early intervention
Substitute prescribing
Rapid
reinstatement
after abstinence
Rapid escalation from single
use to full dependence after
abstinence
Relapse prevention
Salience and
craving
Desire for drug outweighs
need for healthy lifestyle
Proactive follow up via
community services
Desire for drug outweighs
need for medical treatment
Manage
non​concordance
Legal measures
Substitute prescribing
Desire for drug outweighs
need for healthy lifestyle in
pregnancy
Substitute prescribing
Liaison with obstetric
services, primary care,
and substance misuse
specialists

26.5.6 Depressive disorder 6493 Joseph Cerimele an
26.5.6 Depressive disorder 6493 Joseph Cerimele and Lydia Chwastiak
26.5.6  Depressive disorder
6493
who then resume use on discharge, may re-​establish levels of tol-
erance and vulnerability to withdrawal much faster than they ori-
ginally did. For patients frequently admitted to hospital, the cycle
of detoxification and re-​toxification is probably more harmful than
agreeing a more regular substitute prescription regimen, though this
is best undertaken by a specialist substance misuse service rather
than in a medical clinic. Communication with relapse prevention
programmes run by substance misuse services is also important for
newly abstinent patients on discharge from medical wards. Some
hospitals employ drug liaison nurses who act as the link between
medical and substance misuse services, ensuring clear communica-
tion, consistency in prescribing, and proactive follow up.
Attempts to obtain the drug of misuse
The salience of and craving for the drug of dependence can lead to
some of the most difficult substance misuse problems encountered on
medical wards. A patient’s desire to obtain a drug of addiction can be so
strong as to outweigh all other considerations, leading to them taking
major risks with their physical health. Such patients can pressurize
ward teams to prescribe inappropriately and may not adhere to medical
advice. Some patients will self-​discharge from hospital to obtain drugs,
while others may bring drugs into the ward or arrange for them to be
delivered. Patients with direct venous access (peripheral cannulae, cen-
tral lines) may misuse these to self-​administer illicit drugs. These risks
are greatest in patients who are mobile and face lengthy admissions, as
in those on intravenous antibiotics for infectious endocarditis.
Such cases can try the patience of medical teams and may raise the
question of legal interventions, via common law, mental health, or in-
capacity legislation. How such cases are managed will vary between jur-
isdictions, hence it is important for medical teams encountering such
cases to understand what the local law permits, requires, and prevents.
For example, in the three United Kingdom jurisdictions, drug depend-
ence in itself is excluded as grounds for applying incapacity measures
or detention under the mental health act (although abnormal mental
states arising from drug use are not). It is generally preferable to avoid
recourse to legal measures and to offer discussion with the patient,
their family, and relevant drug misuse and psychiatry services.
The guiding principles behind management should be openness
of discussion, clarity of communication, consistency within and
between teams, willingness to set limits, and firmness in applying
them. Even when all these principles are adhered to, there will be
cases where patients take their own discharge to the detriment of
their health, and others where they might be asked to leave the hos-
pital, or even be arrested within it.
Where the risks accrue to someone other than the dependent user,
such as a child, or a fetus, it can be particularly difficult to strike
the balance between intervening too little and too late, and thereby
allowing harm to arise, and intervening too strongly or precipi-
tately and thereby causing it. Liaison with social workers, obstetric
services, and substance misuse specialists is therefore important.
FURTHER READING
Department of Health (England) (2007). Drug misuse and depend-
ence: UK guidelines on clinical management. Department of Health
(England), London; the Scottish Government, Welsh Assembly
Government, and Northern Ireland Executive.
National Institute for Health and Clinical Excellence (NICE) (2007).
Drug misuse:  opiate detoxification. NICE clinical guideline 52.
National Institute for Health and Clinical Excellence, London.
Royal College of Psychiatrists (2014). One new drug a week: why novel
psychoactive substances and club drugs need a different response from
UK treatment providers. Royal College of Psychiatrists, London.
World Health Organization (2010). Mental and behavioural disor-
ders due to psychoactive substance use (F10-​F19) in International
Statistical Classification of Diseases and Related Health Problems,
10th revision (ICD-​10). World Health Organization, Geneva.
26.5.6  Depressive disorder
Joseph Cerimele and Lydia Chwastiak
ESSENTIALS
Depression is a common psychiatric illness seen by physicians. It not
only greatly impairs quality of life, but also frequently complicates
chronic medical conditions such as diabetes. Despite being common
and clinically important it is frequently insufficiently treated, hence it
is important to seek the symptoms of depression in all patients with
chronic medical conditions. When found, the physician has an im-
portant role in explaining the nature of depression and its treatment
to the patient. Treatment is with antidepressant drugs and/​or psy-
chological treatment. When assessing depressed patients, it is always
important to assess for suicide risk. Complex cases, failure to respond
to initial treatment, or concern about suicide risk, indicate the need
for referral to a psychiatrist.
Introduction
Depression is now the leading cause of disability worldwide. The
World Mental Health Survey, conducted in 17 countries, found that
1 in 20 people reported having suffered an episode of depression in
the previous year. Depressive disorders typically start at a young age
and are often recurrent or chronic. They have a severe negative effect
on quality of life (affecting individuals’ ability to work and form re-
lationships), have adverse effects on co-​morbid medical illness, and
increase the risk of suicide. Although efficacious and cost-​effective
treatments are available, most people do not receive them. Barriers
to effective treatment include both a failure to diagnose depression
and a failure to provide effective treatment.
Aetiology
Depression is the product of interactions between genetic vulner-
ability and environmental exposures. The concordance rate for
depression among monozygotic twins was 37% in a large Swedish
study of over 15 000 sets of twins, indicating genetic vulnerability.
Depression is also more likely to develop after negative life stresses
SECTION 26  Psychiatric and drug-related disorders
6494
and in those who lack social support. There is a strong association
with living in an area of social deprivation. Physiologically, de-
pression is associated with dysregulation of noradrenaline (nor-
epinephrine), serotonin, and dopamine and dysfunction of the
hypothalamic–​pituitary–​adrenal (HPA) axis.
Epidemiology
The lifetime prevalence of major depressive disorder in Western
countries is approximately 13%, with a 12-​month prevalence of
5%. The prevalence is higher among women, probably because of
both biological (endocrine), and sociocultural factors. Depression
is a recurrent illness; more than three-​quarters of those who ex-
perience a major depressive episode will experience a subsequent
episode.
Almost half of patients with major depressive disorder have co-​
morbid anxiety disorders, and many have coexisting substance
use problems. In the United States, the estimated total annual
cost of major depressive disorder was $210.5 billion in 2010, with
approximately 45% attributable to direct costs, 5% to suicide-​related
mortality costs and 50% to workplace costs.
Co-​morbid medical conditions account for the largest portion
of the growing economic burden of major depressive disorder.
Persons with cardiovascular disease, diabetes, and other chronic
medical conditions have an increased risk of major depressive dis-
order that complicates the management of the medical condition
(Table 26.5.6.1 and Fig. 26.5.6.1).
Clinical features
Depressed mood and anhedonia (loss of interest and pleasure) are the
two cardinal symptoms of depression. At least one of these must be pre-
sent for at least two weeks for a diagnosis of major depressive disorder.
The diagnosis requires five or more of the following nine symptoms.
•	 Feeling depressed, sad, or hopeless most of the time (depressed
mood)
•	 Loss of interest or pleasure in activities (anhedonia)
•	 Change in appetite and/​ or weight loss or gain (change of >5% of
body weight in a month)
•	 Sleeping more or less than usual (insomnia or hypersomnia)
•	 Physical restlessness (psychomotor agitation) or slowed move-
ments (psychomotor retardation)
•	 Fatigue or loss of energy
•	 Frequent feelings of worthlessness, or excessive or inappropriate
guilt
•	 Diminished ability to concentrate or make decisions
•	 Recurrent thoughts of death or suicidal thought, plans, or an
attempt
Table 26.5.6.1  Twelve-​month prevalence of major depressive
disorder in patients with chronic medical conditions
Population
12-​month prevalence
Community
3–​5%
Primary care
6–​10%
Cardiovascular disease
15–​23%
Diabetes
12–​18%
Chronic pain
33–​35%
Unhealthy behaviours—binge
eating, smoking, etc...
Stress of diabetes
management
Poor symptom control
Difficulty in
exercising/exhaustion
Complications of medical
illness
Mortality
DEPRESSION
DIABETES
Difficulty in making dietary
changes
Lack of social interaction
Lack of adherence to medication
Lack of motivation to
exercise/obesity
Psychophysiologic:      Insulin
sensitivity,    autoimmune
nervous system    inflammatory
makers,   cortisol
Fig. 26.5.6.1  Bidirectional adverse effects of depression and diabetes.
26.5.6  Depressive disorder
6495
Almost half of patients with depression do not have their depres-
sion diagnosed. It is important to remember that most patients
with depression initially present with physical complaints such
as fatigue or poor sleep, rather than with low mood. Because
the diagnosis is often missed, active screening for depression
has been recommended. The Patient Health Questionnaire-​
9 (PHQ-​9) is a self-​rated scale widely used to screen for de-
pression and to monitor response to depression treatment
(Fig. 26.5.6.2).
Treatment
Patients with depression require timely, evidence-​based treatment.
Mild depression benefits from either a psychological intervention
or an antidepressant medication, and moderate or severe depres-
sion from a combination of antidepressant medication and a high-​
intensity psychological treatment.
The first step in treatment is to educate patients about the nature
of depression and its treatment. A collaborative approach with the
PATIENT HEALTH QUESTIONNAIRE-9
(PHQ-9)
Over the last 2 weeks, how often have you been bothered
by any of the following problems?
(Use “    ” to indicate your answer)
Little interest or pleasure in doing things
Not at all
0
1
2
3
0
1
2
3
0
1
2
3
0
1
2
3
0
1
2
3
0
1
2
3
0
1
2
3
0
1
2
3
0
Not difficult
at all
Somewhat
difficult
Very
difficult
Extremely
difficult
FOR OFFICE CODING
If you checked off any problems, how difficult have these problems made it for you to do your
work, take care of things at home, or get along with other people?
0
= Total Score:
1
2
3
Several
days
More
than half
the days
Nearly
every
day
3. Trouble falling or staying asleep, or sleeping too much
Feeling tired or having little energy
Poor appetite or overeating
4.
5.
Feeling bad about yourself—or that you are a failure or
have let yourself or your family down
6.
Thoughts that you would be better off dead or of hurting
yourself in some way
9.
Moving or speaking so slowly that other people could have
noticed? Or the opposite—being so fidgety or restless
that you have been moving around a lot more than usual
8.
Trouble concentrating on things, such as reading the
newspaper or watching television
7.
Feeling down, depressed, or hopeless
2.
Fig. 26.5.6.2  The Patient Health Questionnaire-​9, a behavioural health measure for screening for
depression and monitoring response to treatment.
Developed by Drs. Robert L. Spitzer, Janet B. W. Williams, Kurt Kroenke, and colleagues.
SECTION 26  Psychiatric and drug-related disorders
6496
patient works best and can increase the patient’s sense of participation
in their care, leading to better subsequent adherence to treatment.
Several factors influence the choice of treatment:
•	 Duration of the episode of depression
•	 Previous course of depression and response to treatment
•	 Likelihood of adherence to treatment and any potential adverse effects
•	 The patient’s treatment preference
Psychotherapy
Three effective forms of short-​term psychotherapy or talking treat-
ment commonly used for depression are cognitive behavioural
therapy, interpersonal psychotherapy, and problem-​solving therapy.
Cognitive behavioural therapy addresses negative and distorted
thinking patterns and related behaviours that often accompany de-
pression. Behavioural activation is a simpler type of cognitive be-
havioural therapy that aims to help the patient regain important
activities. Interpersonal psychotherapy targets current interpersonal
relationship difficulties that contribute to the development and per-
sistence of depressive symptoms. Problem-​solving therapy is a col-
laborative treatment in which patient and therapist break down life
problems into smaller, solvable units, and address them one at a time.
Antidepressant medications
Antidepressant medications are all of similar efficacy in the treatment
of outpatients with major depression. Medication choice is therefore
based on factors other than efficacy, such as side effects, history of re-
sponse, or a failure in the individual or a family member, possible drug
interactions, psychiatric or medical co-​morbidity, and patient age.
The selective serotonin reuptake inhibitors (SSRIs) are usually
the first-​line treatment due to their tolerability (Table 26.5.6.2). It
should be noted, however, that most SSRIs inhibit the cytochrome
P450 system in the liver; paroxetine and fluoxetine have the greatest
potential for drug interactions.
Common side effects of SSRIs include anxiety, insomnia, nausea,
and headache. However, these occur to a problematic degree in
fewer than 20% of patients.
Monitoring treatment response
Brief reviews every 2 weeks are needed during the first 6 weeks of
treatment to evaluate side effects of medications and review the
dosage. Treatment response should be assessed after 4 weeks of a
therapeutic dose of medication. Self-​rating scales (such as the PHQ-​
9) administered at initial diagnosis and at each follow-​up offer a
simple way to monitoring response. A 25% or greater reduction in
baseline symptoms constitutes a reasonable basis for extending the
initial treatment. If there has been no response or only a partial re-
sponse, the dose should be increased to the upper therapeutic range.
For patients who still do not respond to treatment, it is im-
portant to:
•	 check adherence to, and side effects from, initial treatment;
•	 increase the frequency of appointments using outcome monitoring;
•	 consider re-​introducing previous treatments that have been inad-
equately delivered or adhered to;
•	 consider switching to an alternative antidepressant;
•	 consider combining with a second drug or augmenting the first
drug.
A change in treatment after non​response (either switching to dif-
ferent SSRI or different class of antidepressant or combining the first
drug with another drug such as mirtazapine) leads to an additional
20% of patients responding. A second change in treatment (either
augmentation or switching) is effective in an additional 10–​15% of
patients.
Switching antidepressants
Switching to another antidepressant can be done within one
week when switching from drugs with a short half-​life. However,
the potential for interactions should be considered when
determining the choice of new drug and the duration of the
transition. Switching may be to a different SSRI or to a newer-​
generation antidepressant (serotonin–​norepinephrine reuptake
inhibitor or mirtazapine).
Combining and augmenting medications
Combination treatment is combining two antidepressants, such
as when mirtazapine is added to SSRI treatment. The use of com-
binations of medications may be needed in some patients, but
increases the risk of potential medication interactions and side
effect burden, and may require specialist advice. Augmentation
involves the use of a non-​antidepressant medication (lithium,
aripiprazole, quetiapine, and thyroxine) with an antidepressant.
Continuation and maintenance therapy
Once recovered from the depressive episode, patients should con-
tinue medication treatment for at least nine months to minimize the
risk of relapse; approximately 40% of remitted primary care patients
suffer relapse.
Stopping treatment
Treatment with antidepressant drugs should generally not be sud-
denly discontinued; almost all antidepressants (except fluoxetine)
can produce discontinuation symptoms (sleep disturbance, anxiety,
memory disturbance, malaise, muscle aches, vertigo, sweating, and
gastrointestinal upset). Discontinuation is therefore done by redu-
cing the dose gradually over several weeks.
Collaborative care
Collaborative care is a system of care in which a psychiatrist col-
laborates with a primary care physician, aided by a case manager.
It is effective in achieving cost-​effective delivery of both drug and
psychological treatments for depression. Table 26.5.6.3 list the prin-
ciples of collaborative care.
Other treatments
Electroconvulsive therapy (ECT) remains the most effective treat-
ment available for very severe or psychotic depression. Some re-
versible short-​term memory loss is a common side effect, but this
reverts to normal in almost all cases. Patients with recurrent depres-
sion who receive effective ECT treatment need prophylactic medi-
cation or maintenance ECT once the acute course of the treatment
has finished.
Meta-​analyses of randomized-​controlled trials suggest that re-
petitive transcranial magnetic stimulation has short-​term anti-
depressant properties.
26.5.6  Depressive disorder
6497
Outcome
Depression is typically a chronic or recurrent illness. Half the patients
who have had a single major depressive episode will have a second
one; 70% of those who have two episodes will have a third; and 90%
of those who have had three episodes will have a fourth.
The number of previous episodes of depression, presence of re-
sidual symptoms, and co-​occurring health problems and social diffi-
culties increase the risk of recurrence. Patients at risk for recurrence
should continue antidepressant medications at the dose used to
achieve remission for at least two years. The potential for severe con-
sequences from recurrent depression, including suicide, are strong
reasons to maintain antidepressant therapy.
The risk of suicide is 10 times greater in patients with depression
compared to the general population; suicide risk should therefore
be assessed in all patients with depression. Most people who
complete suicide have presented to their primary care physician
within a month of their death. Older white males are at highest
risk, and alcoholism, severe medical illness, psychosis, and lack
of social support are additional risk factors. Asking about suicide
will not increase a patient’s risk. Enquiries about suicide can re-
assure the patient and enable the physician and patient together
to make a plan to prevent suicide, including deciding together
whether emergency psychiatric consultation or hospitalization is
necessary.
There is an increased risk of thoughts of suicide in the first 28 days
after starting and stopping antidepressants, so careful monitoring of
patients during these periods is required. Advise a person with de-
pression and their family to be vigilant for mood changes, negativity
and hopelessness, and suicidal ideation, and to contact their practi-
tioner if concerned.
Table 26.5.6.2  Overview of commonly used antidepressant medications
Medication
Common
starting doses
Therapeutic dose
Class
Advantages
Disadvantages
Citalopram
10 mg/​day
20–​40 mg/​day
SSRI
Fewer medication interactions
40 mg is the maximum dose
as higher dose increases risk of
prolonged QTc
Escitalopram
5 mg/​day
10–​20 mg/​day
SSRI
Fewer medication interactions;
less likely to cause sexual side effects
More expensive than citalopram
Fluoxetine
10–​20 mg/​day
20–​80 mg/​day
SSRI
Longer half-​life makes tapering
unnecessary (good for patients with
inconsistent adherence);
relatively weight neutral
More CY P450 interactions
Paroxetine
10–​20 mg/​day
20–​60 mg/​day
SSRI
Sedating effects helpful for anxiety
and insomnia
Gastrointestinal side effects;
anticholinergic effects increase
fall risk and confusion in older
people
Sertraline
25–​50 mg/​day
100–​200 mg/​day
SSRI
Safe to use post-​MI
Few
Mirtazapine
7.5–​15 mg /​day
30–​45 mg/​day
SNRI at
therapeutic dose
Sedating effects helpful for anxiety
and insomnia
Sedation;
increased appetite and weight
gain
Venlafaxine
37.5–​75 mg /​day
150–​300 mg/​day
SNRI
Helpful for neuropathic pain;
XR version can be taken once daily
Risk of increase diastolic blood
pressure;
short half-​life can cause an
uncomfortable discontinuation
syndrome
Duloxetine
20 mg /​day
60–​90 mg/​day
SNRI
Effective for treatment of peripheral
neuropathy and fibromyalgia
Dose adjustment for CrCl
<30 ml/​min;
expensive
SNRI, serotonin–​norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.
Table 26.5.6.3  Core principles of collaborative care
Core principle
Definition
Patient-​centred team care
Primary care and psychiatrists collaborate using shared care plans that incorporate patient goals.
Population-​based care
Care team shares a defined group of patients tracked in a registry to ensure no one falls through the cracks.
Measurement-​based treatment to target (or
stepped care)
Each patient has a target; progress toward this is monitored and treatment changed if patients are not improving.
Evidence-​based care
Patients are given evidence-​based care (both drugs and psychotherapies).

26.5.7 Bipolar disorder 6498 Kate E.A. Saunders an
26.5.7 Bipolar disorder 6498 Kate E.A. Saunders and John Geddes
SECTION 26  Psychiatric and drug-related disorders
6498
FURTHER READING
Archer J, et al. (2012). Collaborative care for depression and anxiety
problems. Cochrane Database Syst Rev, 10, CD006525.
Katon WJ (2011). Epidemiology and treatment of depression in pa-
tients with chronic medical illness. Dialogues Clin Neurosci, 13, 7–​23.
Katon WJ, et al. (2010). Collaborative care for patients with depression
and chronic illnesses. N Engl J Med, 363, 2611–​20.
National Institute for Health and Care Excellence (NICE) (2009).
Depression in adults: recognition and management. Clinical guide-
line [CG90]. Last updated:  April 2016. https://​www.nice.org.uk/​
guidance/​CG90
National Institute for Health and Care Excellence (NICE) (2009).
Depression in adults with a chronic physical health problem: recogni-
tion and management. Clinical guideline [CG91]. https://​www.nice.
org.uk/​guidance/​CG90
26.5.7  Bipolar disorder
Kate E.A. Saunders and John Geddes
ESSENTIALS
Bipolar disorder is a highly heritable, lifelong, relapsing, and remitting
chronic mental illness. While traditionally characterized as a disorder
with distinct periods of elated and depressed mood, it is now clear
that interepisode mood instability is common. Comorbid psychiatric
and medical conditions are common. When occurring in medical
settings mania can be both disruptive and hazardous, and may re-
quire active psychiatric management. Pharmacological approaches
are the mainstay of treatment, although adjunctive psychotherapies
are helpful in preventing relapse. Compulsory detention in hospital
using mental health law may sometimes be required for both manic
and depressive states.
Introduction
Bipolar disorder is a chronic recurrent mood disorder, previously
known as manic-​depressive illness. It is characterized by un-
stable mood with periods of both depressed and elevated mood.
Bipolar disorder is classified into three subtypes: bipolar I which
is characterized by the presence of mania (Box 26.5.7.1), bipolar
II which is characterized by hypomania (Box 26.5.7.2), and bi-
polar not otherwise specified (NOS) which is used to describe
those who do not fulfil the duration criteria for hypomania/​
mania or where there is little discernible effect on the individual’s
functioning.
Aetiology
The main cause of bipolar disorder is genetic, although environ-
mental factors also play a role. The heritability (the extent to which
the disorder can be accounted for by genetic factors) is estimated
to be 85%. People with a first-​degree relative with bipolar disorder
have a 14-​fold increased risk of developing the condition. Genome-​
wide association studies have identified association with several
common genetic polymorphisms with considerable overlap in sus-
ceptibility with other disorders, including schizophrenia, but as yet
there are no valid biomarkers.
Epidemiology
Bipolar I and bipolar II disorders affect around 2% of the popula-
tion, with subthreshold forms present in a further 2%. The mean
age of onset in community studies is 17 years. However, delays in
the initial diagnosis are common, hence it is possible that the age
of onset has become earlier since the 1990s. This may reflect in-
creased use of antidepressants and stimulants precipitating epi-
sodes of mania, or simply be attributable to greater awareness of
the diagnosis.
The prevalence of bipolar disorder is similar in males and
females. An early age of onset is heritable and associated with
poorer prognosis. The diagnosis of bipolar disorder in children
has increased in recent years, especially in the United States, but
the persistence of this increased rate of diagnosis into adulthood
remains unclear as no comparable increase in adults has been
observed.
Clinical features
The key feature of bipolar disorder is the occurrence of manic or
hypomanic episodes. There are usually also episodes of depression
(Fig. 26.5.7.1).
Box 26.5.7.2  Features of hypomania
•	 Symptoms as described for mania
•	 A minimum duration of four days
•	 A change in functioning, but not one severe enough to severely impair
functioning or to necessitate hospitalization
Box 26.5.7.1  Features of mania
A period of abnormally and persistently elevated, expansive, or irrit-
able mood, lasting at least one week (or any duration if hospitalization
is necessary)
Additional symptoms that include
•	 Inflated self-​esteem or grandiosity
•	 Decreased need for sleep
•	 More talkative than usual or pressure to keep talking
•	 Flight of ideas or a subjective experience that thoughts are racing
•	 Distractibility
•	 Increase in goal-​directed activity (either socially, at work or school,
or sexually)
•	 Agitation
•	 Risky behaviour (e.g. rash purchases and sexual indiscretion)
26.5.7  Bipolar disorder
6499
Mania and hypomania
A manic episode is a distinct period of abnormality of mood of at
least a week’s duration that is severe enough to cause social or occu-
pational difficulty or to lead to hospital admission. Mood is persist-
ently elevated, expansive, or sometimes irritable. Other symptoms
include persistently increased activity or energy and commonly a
reduced need for sleep. The patient may appear unusually talkative,
with rapid speech, and be unusually distractible. They may express
inflated or grandiose ideas about their ability or status, and may be-
have in an unwise or risky way such as spending excessively. If the
mania is severe, there may also be delusions and hallucinations, the
context of which is typically grandiose and in keeping with the ele-
vated mood. There is no reduction of conscious level as with organic
brain states. A hypomanic episode is a noticeable but less disruptive
period of elevated mood.
Depression
The core symptoms of depression are low mood and/​or anhedonia
(loss of interest or pleasure in activities). In contrast to mania, with-
drawal and reduced energy are common. Speech may be slow and
ideas of low self-​worth, pessimism, and even suicide expressed.
Sleep is commonly disturbed and in bipolar depression may take
the form of increased rather than reduced or disrupted sleep.
A period of depressed mood typically occurs after an episode of
elevated mood.
Differential diagnosis
The diagnosis of bipolar disorder requires a history of (hypo) manic
symptoms. The main medical differential diagnosis for mania or
hypomania is intoxication with stimulant drugs such as cocaine or
amphetamines and from other organic brain states. These include
delirium from any cause, where there is typically clouding of con-
sciousness, and occasionally head injuries, brain tumours, or epi-
lepsy. The psychiatric differential includes cyclothymic and other
personality disorders, and the main alterative diagnosis is schizo-
phrenia if there are persistent hallucinations or delusions in a clear
consciousness.
For presentations with symptoms of depression, the main dif-
ferential diagnosis is from unipolar depression. Bipolar disorder is
commonly initially misdiagnosed as unipolar depression.
Psychiatric comorbidity
Other psychiatric disorders commonly co-​occur with bipolar dis-
order, particularly with bipolar II. Sixty-​five per cent (65%) of people
with bipolar disorders have at least one comorbid psychiatric dis-
order, with many having two or more. Anxiety disorders are the
most common and are associated with higher rates of suicide, al-
cohol misuse, and a poorer response to lithium. Alcohol misuse is
common. Personality disorders are present in between 25% and 50%
of patients, although these estimates are imprecise as most studies
20
10
5
0
20
10
5
0
20
30
40
Weeks
Mood scores
Mood scores
50
10
0
20
30
40
Weeks
50
10
0
20
10
5
0
Mood scores
20
30
40
Weeks
50
10
0
20
10
5
0
20
10
5
0
20
30
40
Weeks
Mood scores
Mood scores
50
10
0
20
30
40
Weeks
50
10
0
20
10
5
0
Mood scores
20
30
40
Weeks
50
10
0
Fig. 26.5.7.1  Examples of mood instability in six patients with bipolar disorder in the
OXTEXT cohort (data anonymized), as captured by prospective mood monitoring using
the True Colours system (http://​oxtext.psych.ox.ac.uk/​).
Blue line: scores for depressive symptoms as rated with the Quick Inventory of Depressive Symptoms
(http://​www.ids-​qids.org/​). Red line: scores for manic symptoms as rated with the Altman Self-​Rating
Mania Scale (http://​www.cqaimh.org/​pdf/​tool_​asrm.pdf).
SECTION 26  Psychiatric and drug-related disorders
6500
have sought to establish the presence of personality disorder in the
presence of ongoing mood symptoms. Comorbid personality dis-
order is associated with poorer treatment response, greater sub-
stance misuse, and a worse prognosis.
Medical comorbidity
Bipolar disorder is associated with coexisting medical illness. The
most prevalent are migraine, asthma, elevated lipids, hyperten-
sion, thyroid disease, and osteoarthritis. Genome-​wide association
studies suggest that the bipolar disorder and metabolic disorders
such as type II diabetes have common genetic links and may share
pathophysiological pathways.
Treatment
The treatment of bipolar disorder is done in two stages: first, treat-
ment of acute affective episodes, and second, maintenance treat-
ment. See Table 26.5.7.1.
Acute mania
Current evidence favours the use of antipsychotic medication in the
initial treatment of mania. For this purpose, antipsychotic drugs are
superior to lithium or carbamazepine. Risperidone, olanzapine, and
haloperidol have the best efficacy and tolerability. If a patient is al-
ready taking a mood stabilizing agent such as lithium, the dose of
this should be optimized.
Acute depression
The treatment of bipolar depression is a challenge with few ef-
ficacious treatments. A  recent meta-​analysis of the efficacy of
antidepressants found no efficacy. However, antidepressants
are heterogeneous in terms of mechanism of action, tolerability
and efficacy, and it may be premature to conclude that none is
of any use. There is also a risk that antidepressant monotherapy
in the absence of an antimanic treatment may precipitate mania
or greater mood instability. This risk can be reduced by only
using antidepressants in combination with a mood stabilizer or
antimanic agent.
Some atypical antipsychotics, such as quetiapine and olanzapine
(in combination with fluoxetine), and lurasidone are effective in bi-
polar depression, as well as having an antimanic effect. Lamotrigine,
an antiepileptic drug, also appears to be effective in bipolar depres-
sion. Drugs used solely for acute treatment should be tapered over
several weeks once the patient is in remission.
Maintenance treatment
Drug treatment
Lithium is the mainstay of maintenance treatment in bipolar dis-
order. It has been in use ever since its discovery by John Cade in
1949. Most of the evidence for its efficacy comes from randomized
controlled trials of atypical antipsychotics in which lithium was
an active comparator. Its use is limited by its narrow therapeutic
window, adverse effects, and toxicity in overdose. Lithium is as-
sociated with renal impairment in a small but significant number
of people, although the relationship with end stage renal failure is
not established. The risk of decline in renal function is greatest in
younger women and in those with higher serum lithium concen-
trations. Thyroid, parathyroid, and calcium metabolism can all be
affected and must be monitored, both before and during treatment.
In pregnancy, there is a possible risk of fetal cardiac malformations.
A decision to withdraw lithium during pregnancy needs to consider
both the risk to the fetus and the risk of relapse in the mother.
The use of sodium valproate has dramatically increased in recent
years despite the paucity of evidence from randomized controlled
trials. The BALANCE trial found that lithium monotherapy was
better than valproate monotherapy in preventing mood episodes,
and combined treatment with lithium and valproate is better than
valproate monotherapy. Valproate is associated with neural tube de-
fects so is not recommended for use in women of childbearing age.
Lamotrigine appears more effective than placebo in preventing
depressive or manic episodes and has comparable efficacy to lithium,
although adverse events are more common with lithium.
There is only weak evidence that antipsychotic drugs are ef-
fective in prevention, although quetiapine appears to be effective in
preventing the recurrence of depressive episodes.
Most patients will require maintenance treatment for many years;
discontinuing stable treatment often leads to the emergence of a new
episode of mood disturbance. Of those taking lithium more than
half experience a recurrence within 10 weeks of discontinuation and
approximately 90% within a year. Slow withdrawal of medication is
associated with a lower rate of recurrence.
One of the challenges in the treatment of bipolar disorder is the
gap between the evidence, which mostly concerns single treatments,
and clinical practice where polypharmacy is common. Almost all
patients are taking more than one agent. Adherence is often poor
and those with comorbid personality disorders, substance misuse,
and greater illness severity are more likely to stop medication.
Psychological treatment
Although pharmacotherapy is the mainstay of treatment, psy-
chotherapy has a role in improving adherence to drug treatment
and in preventing relapses. The main goals of this adjunctive psy-
chotherapy are to educate patients and caregivers and improve
adherence to pharmacotherapy. There is also a role for stress
management, the identification of triggers, and signs of relapse
and strategies to maintain regular patterns of sleep and activity
(see Box 26.5.7.2). Cognitive behavioural therapy, family fo-
cused therapy, interpersonal and social rhythm therapy, group
psychoeducation, and systematic care management all have evi-
dence to support their use in bipolar disorder, although which
specific ingredients of these complex treatments is effective re-
mains unclear (Box 26.5.7.3).
Table 26.5.7.1  Treatment of bipolar disorder
Acute mania
Stop antidepressant (if currently taking one)
Offer an antipsychotic drug
Optimize lithium/​mood stabilizer if already taking this
Acute depression
Offer quetiapine OR olanzapine and fluoxetine
Offer lamotrigine alone or in combination with
quetiapine
Maintenance
Lithium
Consider adding valproate to lithium
If previous response in an acute episode consider
quetiapine

26.5.8 Anxiety disorders 6501 Ted Liao and Steve E
26.5.8 Anxiety disorders 6501 Ted Liao and Steve Epstein
26.5.8  Anxiety disorders
6501
Adjunctive psychotherapy may enhance remission from acute de-
pressive episodes but is not helpful during mania because patients
often reject help and lack insight into their difficulties.
Outcome
The presenting type of mood disorder is familial and may have prog-
nostic significance; a presentation with just mania has the best out-
come. Once established, the characteristic pattern of episodes for
that individual tends to recur. The occurrence of four or more mood
episodes per year is referred to as rapid cycling, which occurs in be-
tween 12% and 24% of people with bipolar disorder and is associ-
ated with earlier age of onset, more comorbid substance misuse, and
more severe depressive episodes.
As most people with bipolar disorder present with a depressive
episode, 40% initially receive a diagnosis of unipolar depression. The
rate of switching from a diagnosis of unipolar disorder to one of bi-
polar disorder is higher in younger people and plateaus at 1% per
year by the age of 30.
Bipolar disorder is a chronic illness, with a 40-​year follow-​up
finding that only 16% had recovered (no episode in the last five
years) and over 50% were experiencing recurrent episodes. The per-
sistence of depressive symptoms is associated with poorer prognosis.
There is also increasing evidence that significant impairment per-
sists even in remitted states.
On average people with bipolar disorder die nine years earlier
than the rest of the population. Suicide risk is increased 10-​fold
in women and 8-​fold in men. Suicide tends to occur early in the
course of the illness, and between 25% and 50% attempt suicide at
least once. Attempts are more likely in depressed and mixed affective
states.
Special circumstances
Pregnancy
Pregnancy and specifically the post-​partum period is a high-​risk
period for women with bipolar disorder when as many as half
relapse. Many of these relapses are depressive in nature and are
most likely to occur in the first trimester, in women who have
bipolar II disorder and in those who have discontinued medi-
cation. The risk of relapse is especially high in the post-​partum
period. There is a need to balance the risk of pharmacotherapy
to the unborn fetus against the risk of recurrence of an affective
episode in the mother.
FURTHER READING
BALANCE investigators, et al. (2010). Lithium plus valproate com-
bination therapy versus monotherapy for relapse prevention in
bipolar I  disorder (BALANCE):  a randomised open-​label trial.
Lancet, 375, 385–​95.
Craddock N, Sklar P (2013). Genetics of bipolar disorder. Lancet, 381,
1654–​62.
Geddes JR, Miklowitz DJ (2013). Treatment of bipolar disorder.
Lancet, 381, 1672–​82.
Grande, I, et al. (2015) Bipolar disorder. Lancet, 387, 1561–​72.
McKnight RF, et al. (2012). Lithium toxicity profile: a systematic re-
view and meta-​analysis. Lancet, 379, 721–​8.
Phillips ML, Kupfer DJ (2013). Bipolar disorder diagnosis: challenges
and future directions. Lancet, 381, 1663–​71.
26.5.8  Anxiety disorders
Ted Liao and Steve Epstein
ESSENTIALS
Anxiety is a common feeling, but also the central symptom of several
psychiatric disorders:  generalized anxiety disorder, panic disorder,
phobias, and obsessive-​compulsive disorder. Anxiety disorders are
common and important in general medical practice as they often
manifest with physical symptoms such as palpitations, chest pain,
and dizziness that can be misdiagnosed as medical conditions and
lead to unnecessary investigation and treatment. Anxiety disorder,
especially phobic anxiety, can also lead to inability to adhere to med-
ical treatments, for example, because of needle phobia interfering
with blood tests and/​or injected drugs treatment. Both pharmaco-
logical and psychological treatments are effective. For chronic anx-
iety, selective serotonin reuptake inhibitors are the drugs of choice,
with benzodiazepines being reserved for short-​term use. If available,
cognitive behaviour therapy is similarly effective. Anxiety disorders
usually respond to treatment but often recur.
Introduction
Feeling anxious is both a normal and common human experience.
Words such as worry, nervousness, and apprehension all describe
this everyday emotion. Normal worry can serve an adaptive func-
tion, motivating individuals to take action to avoid negative con-
sequences (e.g. studying for a test to avoid failing it) and can be an
ordinary response to stressful situations (e.g. anxiety related to an-
ticipated loss of independence following illness).
Patients with anxiety disorders suffer from more than normal
worry. They experience more pervasive and persistent anxiety, as
well as other psychological and physiological symptoms. The se-
verity of these is such that there is significant functional impairment.
Whereas normal worry can spur people to action, anxiety disorders
can cripple them.
Box 26.5.7.3  Psychological treatment of bipolar disorder
•	 Enhance ability to identify warning signs of recurrence and intervene
early
•	 Increase acceptance of illness
•	 Enhance adherence to prescribed medication
•	 Improve resilience to environmental stressors associated with
symptoms
•	 Stabilize sleep patterns and other daily routines
•	 Enhance family relationships and communication
•	 Reduce drug and alcohol misuse
Adapted from Geddes & Miklowitz (2013).
SECTION 26  Psychiatric and drug-related disorders
6502
Untreated, anxiety disorders can impair a patient’s ability to ad-
here to medical treatments, and as a result can have negative reper-
cussions on a patient’s overall health and quality of life. Appropriate
diagnosis and treatment of anxiety disorders can reduce morbidity,
minimize disability, and restore functionality.
Aetiology
Both genetic and psychosocial factors contribute to the aetiology of
anxiety disorders. Estimates of heritability range from 15% to 50%.
Early-​life influences (e.g. parents with anxiety) can exert a lasting
influence on how patients respond to stressors. The brain regions
most strongly implicated in the pathogenesis of anxiety disorders
are the amygdala, the insular cortex, the cingulate cortex, and the
prefrontal cortex. The neurotransmitters most strongly associated
with anxiety disorders are γ-​aminobutyric acid, serotonin, and
norepinephrine.
Epidemiology
Anxiety disorders are very common. Approximately one in five
adults suffer from an anxiety disorder according to large popula-
tion surveys performed in several international settings. Onset is
commonly in childhood and adolescence. Anxiety disorders dis-
proportionately affect women and are associated with high rates of
disability. Patients with anxiety disorders frequently seek treatment
in primary and specialty medical care settings, often initially pre-
senting with physical symptoms.
Clinical features
The presenting complaints of patients with anxiety disorders can
vary widely. The main psychological symptom of anxiety disorders is
feeling anxious, tense, fearful, or agitated. Worry about future events
is common. The associated behaviours include avoidance of feared
situations and compulsive behaviours that serve to reduce the anx-
iety (Table 26.5.8.1).
Importantly, anxiety can also present with physical symptoms.
These include fatigue, aches and pains, poor sleep, palpitations,
breathlessness, dizziness, and chest pain. Episodic sudden onset of
many physical symptoms suggests panic attacks. Common physical
symptoms are listed in Table 26.5.8.2.
Specific anxiety disorders
Table 26.5.8.3 describes the key features of the specific anxiety
disorders.
Generalized anxiety disorder
Generalized anxiety disorder (GAD) can be distinguished from
other anxiety disorders by its lack of focus on a particular topic (in
contrast with specific phobia or OCD), and by the long, consistent
amount of worry (in contrast with circumscribed panic attacks).
Panic disorder
The most salient feature of panic attacks is their severity and short
duration:  they peak and typically resolve within minutes. Many
patients have some familiarity with the concept of a panic attack
and mistakenly describe other anxiety symptoms as panic attacks.
Accurately eliciting a history of panic attacks is the crucial step in
distinguishing panic disorder from other anxiety disorders.
Not every patient who has a panic attack should be diagnosed with
panic disorder. The hallmark of panic disorder is not simply the pres-
ence of panic attacks, but also a persistent worry about future attacks
and/​or the actions taken to avoid future attacks. Agoraphobia (fear/​
avoidance of crowds, open spaces, or enclosed places) represents one
such maladaptive response to the experience of panic attacks.
Specific phobia
Many individuals are afraid of some of the objects or situations (e.g.
needles) that are the focus of specific phobias, but those individ-
uals perceive an intensity of distress in excess of social norms. One
category of phobias with particular relevance to clinicians is blood-​
injection-​injury phobia. This consists of specific aversions to blood,
needles, or other invasive medical procedures. Specific phobias of
this type may prevent patients from receiving other necessary med-
ical care, and thus warrant prompt diagnosis and treatment.
Table 26.5.8.1  Psychological symptoms of anxiety disorders
Fear (distress about a concrete, imminent stressor)
Anxiety (worry about abstract, future stressors)
Other
psychological
symptoms
Mood
Sense of restlessness
Irritability
Derealization (feelings of unreality)
Depersonalization (feelings of being
detached from oneself)
Cognitive
Worry and obsessional thoughts
Impaired concentration
Behaviour
Avoidance
Compulsive behaviours
Table 26.5.8.2  Common physical symptoms of anxiety disorders
Constitutional
Fatigue
Insomnia
Diaphoresis
Chills
Neurological/​musculoskeletal
Headache
Vertigo
Dizziness and light-​headedness
Unsteadiness
Neck pain
Muscle tension
Tinnitus
Paraesthesia
Tremulousness or tremor
Cardiopulmonary
Chest pain
Palpitations
Tachycardia
Dyspnoea
Gastrointestinal
Nausea
Abdominal pain
26.5.8  Anxiety disorders
6503
Social anxiety disorder (social phobia)
Social anxiety disorder is a phobia of social situations. The distinc-
tion between simple shyness and social phobia depends on severity
and the effect on the person’s life. For instance, a person with normal
shyness may keep to herself or himself at a large social gathering,
but interact more openly with close friends, whereas a person with
social anxiety disorder may avoid social functions altogether and
consequently become socially isolated. Patients with social anxiety
often self-​medicate with alcohol, leading to an association with al-
cohol misuse disorders.
Obsessive-​compulsive disorder
Most patients with obsessive-​compulsive disorder experience both
obsessions and compulsions. It is important to note that the clin-
ical definition of the term ‘obsession’ in the context of obsessive-​
compulsive disorder (OCD) differs from the lay meaning of the
term. The obsessions in OCD are not voluntarily experienced and
are not a source of pleasure; rather they are persistent, unwanted,
and aversive. For example, a woman had obsessions that the food in
her home was rotten.
Compulsions similarly do not bring patients pleasure, merely
temporary relief from the distress associated with the obsessions.
They are also not realistically related to the obsessions that drive
them, or are clearly excessive. For instance, in the aforementioned
case, the woman could only relieve her anxiety by ritualistically
checking and rechecking the expiration date on every food item in
her kitchen.
Assessment of the patient with OCD must include a determin-
ation of the time spent on obsessions and/​or compulsions in order to
determine symptom severity and degree of functional impairment.
The woman mentioned here spent 90 minutes every evening com-
pulsively checking her food instead of going to her evening class,
making the behaviour clearly abnormal.
Differential diagnosis
Anxiety is most commonly understandable and situational. For ex-
ample, seeing a physician to hear whether a serious disease such as
cancer has progressed will cause many patients anxiety. Sometimes,
however, the severity and persistence of anxiety means it is con-
sidered a psychiatric disorder as described here.
Other psychiatric differentials to consider are alcohol or drug
withdrawal, developing delirium or dementia, and occasionally
anxiety secondary to the delusions and hallucinations of a psychotic
disorder.
Some medical conditions can present with symptoms of anxiety
(Table 26.5.8.4). There should be increased suspicion of these and
other medical causes of anxiety if a patient is over 35 with no per-
sonal or family history of anxiety, has no history of using the sub-
stances and medications listed here, lacks significant stressors, and if
standard pharmacological treatment of anxiety fails.
Anxiety may also be a result of prescribed medication. Table
26.5.8.5 lists several substances and medications for which ingestion
or withdrawal may produce significant anxiety. Particular emphasis
should be paid to screening for stimulant ingestion and withdrawal
from ethanol or benzodiazepine use.
Assessment
Detection
Anxiety disorders cause a wide variety of physiological symptoms.
Table 26.5.8.2 lists these symptoms, grouped by bodily system.
Awareness of this form of presentation reduces the risk of mis-
diagnosing anxiety as a medical disorder. It can also help prevent
Table 26.5.8.3  Features of specific anxiety disorders
Generalized
anxiety disorder
(GAD)
–​ Excessive anxiety and worry about multiple issues that is difficult to control.
–​ Occurs more days than not for at least six months.
–​ Associated with some of the following: impaired concentration, irritability, muscle tension, insomnia, and fatigue.
Panic disorder
–​ Recurrent panic attacks: surges of intense fear or anxiety that peak within minutes, associated with palpitations, diaphoresis, tremulousness,
dyspnoea, chest pain, nausea, abdominal pain, dizziness, or paraesthesias.
–​ Associated fear of collapse or death.
–​ Persistent concern about future attacks.
Specific phobia
–​ Marked fear or anxiety about a specific object or situation (e.g. flying, heights, animals, seeing blood), which is actively avoided if possible.
– The fear or anxiety is out of proportion to the actual danger.
–​ These symptoms persist for six months or more.
Obsessive-​
compulsive
disorder (OCD)
–​ Obsessions are persistent, distressing thoughts that are unwanted.
–​ Compulsions are repetitive behaviours or mental acts, rigidly performed to prevent or reduce distress. They are not however connected in a
realistic way with what they are designed to prevent, or are clearly excessive.
–​ Symptoms consume more than one hour per day or cause impairment.
Social phobia
–​ Significant recurrent anxiety about one or more social situations related to scrutiny by others, out of proportion with the actual threat posed,
which causes avoidance and lasts for six months or more.
–​ Associated fears about outwardly showing symptoms of anxiety.
Table 26.5.8.4  Other medical conditions that may cause anxiety
Common
Thyroid dysfunction
Asthma or other pulmonary disease
Electrolyte abnormality (e.g. hypercalcaemia)
Anaemia
Diabetes
Cardiac disease (e.g. tachyarrhythmias)
Delirium (in hospital settings)
Less common
Pheochromocytoma
Other endocrine conditions (e.g. hypogonadism)
Brain neoplasm or metastases
SECTION 26  Psychiatric and drug-related disorders
6504
missed medical diagnoses in patients with concurrent anxiety by
highlighting those symptoms (e.g. diplopia) that are unlikely to be
due to anxiety. The two-​item Generalized Anxiety Scale (GAD-​2)
can be administered as a rapid screening measure for anxiety dis-
orders (Table 26.5.8.6). It is important to note that anxiety com-
monly coexists with depression and that all anxiety patients should
be assessed for depression.
Diagnosis
When a patient is anxious, it is important to first ask how persistent
and severe the anxiety is. To determine the associated functional im-
pairment, the clinician must assess the patient’s level of function in
multiple areas of their life (work, romantic, and family relationships,
friendships, hobbies, and so on). For patients whose level of func-
tioning is poor, also asking about functional level prior to the onset
of symptoms can help establish the extent to which anxiety is con-
tributing to functional impairment.
Treatment
When a medical patient is anxious, the first step is to ask them why
and see if information and addressing their fears, for example, about
prognosis, is effective.
Anxiety disorders, while highly common and frequently
debilitating, are usually treatable. Both drug and psychological treat-
ment are effective and may be used in combination, especially for
severe anxiety disorders.
Pharmacotherapy
Drugs used to treat anxiety disorders are listed in Table 26.5.8.7.
The most commonly used drugs are now the serotonin reuptake in-
hibitors, which while also used as antidepressants have proven to be
even more effective for the treatment of anxiety. Benzodiazepines
such as diazepam and lorazepam are highly effective in relieving
anxiety, but these agents are now generally restricted to short-​term
use because of the risk of dependence.
While many physicians are more comfortable prescribing medi-
cation than providing psychotherapy, it is important to ask the pa-
tient what their preference is. For mild to moderate anxiety, either
modality may be effective as a first-​line treatment. For patients with
moderate to severe anxiety, pharmacotherapy on a short-​ or long-​
term basis is usually needed.
Serotonin reuptake inhibitors
The serotonin reuptake inhibitors are now first-​line treatment for
anxiety disorder. There is no clear difference in efficacy among
these agents, but side effect profiles differ. Many anxious patients
are highly sensitive to medications, so it is important to start slowly
and provide education about the frequency of side effects and time
course of response, in order to avoid premature discontinuation.
Patients need to understand that these medications must be taken
daily, and are not effective on an ‘as-​needed’ basis.
Every physician should become comfortable using a few selective
serotonin reuptake inhibitors (SSRIs) as some patients may prefer
one or have had a prior good or poor response to a particular agent.
Most are now available as generics. They can all be given once daily
making adherence relatively easy.
The most common side effects of SSRIs are gastrointestinal and
sexual. Many patients will experience initial gastrointestinal dis-
comfort including nausea, but it is important to reassure the patient
that this side effect disappears for almost everyone within the first
week of treatment. They should be told to take the medication with
food, at least until the gastrointestinal side effects have remitted.
For some patients, it may be beneficial to start at a lower than usual
starting dosage and titrate up once the gastrointestinal side effects
abate (e.g. starting at sertraline 25 mg daily).
Sexual side effects include decreased interest and anorgasmia for
women and erectile or ejaculatory dysfunction for men. These side
effects do not dissipate but are fully reversible upon discontinuation.
If a patient has benefited from an SSRI and wants to continue it des-
pite these effects, it may be helpful to use PDE5 inhibitors such as
sildenafil or tadalafil. Some may benefit from the addition of bu-
propion 100–​200 mg daily. For those who do not want to continue
an SSRI because of sexual side effects, mirtazapine is an alternative.
It is important to monitor response and not settle for only partial
improvement. If after four to six weeks of treatment there has not been
substantial improvement, the dosage can be increased. If there is still
no improvement, alternative agents or psychotherapy may be needed.
Abrupt discontinuation of SSRIs may cause an uncomfortable
withdrawal state, characterized by insomnia, anxiety, agitation, and
sometimes electric-​like sensations. Patients need to be educated not
Table 26.5.8.6  The two-​item Generalized Anxiety Scale (GAD-​2)
Over the past two weeks, how often have you been bothered by the
following problems?
Feeling nervous, anxious, or on edge
Not at all = 0
Several days = 1
More than one-​half of the
days = 2
Nearly every day = 3
Being unable to stop or control
worrying
Not at all = 0
Several days = 1
More than one-​half of the
days = 2
Nearly every day = 3
Two-​item total score of greater or equal to 3 represents a positive screen.
Table 26.5.8.5  Substances and medications relevant to the
assessment of anxiety
Use may cause anxiety
Prescription stimulants (e.g. methylphenidate)
Cocaine
Caffeine
Cannabinoids
Antidepressants
Corticosteroids (including asthma inhalers)
β2-​adrenergic agonists (including asthma
inhalers)
Androgens or oestrogens
Sympathomimetics (e.g. ephedrine)
Opioid antagonists (due to precipitated
withdrawal)
Withdrawal may cause
anxiety
Ethanol
Benzodiazepines
Barbiturates
Opiates
26.5.8  Anxiety disorders
6505
to stop an SSRI abruptly and that they should be tapered over weeks
under the supervision of a physician.
Pharmacologic treatment for panic disorder should continue for
at least six months after the symptoms have resolved. For patients
with chronic or recurrent panic disorder, or years of generalized
anxiety disorder, treatment may continue indefinitely. Some patients
may be reluctant to taper off if there are ongoing severe psychosocial
stressors. Long-​term treatment with SSRIs is generally quite safe
and late side effects do not occur. The physician should always care-
fully monitor medical conditions and concurrent medications when
SSRIs are given for a long duration (e.g. if a healthy patient develops
peptic ulcer disease this should lead to reconsideration of SSRI use,
given their potential for causing gastrointestinal bleeding).
Other agents
Benzodiazepines, while still widely used, should not usually be first
line for an anxiety disorder as they can cause sedation and cognitive
dysfunction, are addictive, and commonly abused. However, they
are useful for short-​term anxiety, such as that associated with a med-
ical procedure. They may also be used in the occasional patient who
is refractory to treatment with SSRIs, and without a history of al-
cohol or drug abuse.
For a patient with significant anxiety, it may be useful to start an
SSRI and daily benzodiazepine. After a few weeks when the SSRI has
had time to become effective, the benzodiazepine can be gradually
tapered off.
The serotonin and norepinephrine reuptake inhibitors venlafaxine
and duloxetine are usually effective alternatives for anxiety. They
may be preferentially indicated for patients with comorbid pain
such as neuropathic pain or fibromyalgia. Blood pressure should be
checked as they may cause mild increases. Duloxetine rarely causes
hepatic dysfunction.
Other drugs sometimes used to treat anxiety are gabapentin and
pregabalin. Atypical antipsychotic drugs such as quetiapine are also
effective. β-blockers are often prescribed but are only useful in redu-
cing the physical symptoms of performance anxiety.
Psychological treatments
Where available, psychotherapy is the treatment of choice for many
patients with anxiety disorders. The physician can offer brief psy-
chological interventions themselves that are often effective, particu-
larly for those with mild to moderate anxiety. Cognitive behavioural
therapy (CBT) is effective for most anxiety disorders. For patients with
generalized anxiety and panic disorder, the primary care physician
can use elements of CBT. For example, they may encourage patients
to question fearful thoughts, replacing undue fears with more realistic
appraisals, and listing the worst possible scenarios in order to help the
patient see that they can handle feared future events. CBT-​type treat-
ment is increasingly available as internet-​based self-​treatment and
may be useful when access to a therapist is difficult.
Referral for specialized treatments
Patients should be referred for consultation or treatment with a
psychologist or psychiatrist for severe or refractory symptoms, pa-
tient preference, or selected disorders that are generally beyond the
expertise of the primary care physician (Table 26.5.8.8).
Obsessive-​compulsive disorder can be challenging, and psychiat-
rists and other mental health professionals who are expert in CBT
should generally treat it. All of the SSRIs are beneficial, but may need
to be given at higher doses than for generalized anxiety disorder
Table 26.5.8.7  Medications to treat anxiety
Class
Examples
When to use
Selected side effects
Additional notes
Serotonin reuptake inhibitor
Sertraline, escitalopram
First line for anxiety
disorders
Sexual, gastrointestinal, sedation
Serotonin and norepinephrine
reuptake inhibitor
Venlafaxine, duloxetine
First line for anxiety
disorders
Sexual, gastrointestinal
May also help with pain
Tricyclic antidepressant
Nortriptyline, imipramine
Second line
Cardiac, anticholinergic, sedation
Benzodiazepines
Lorazepam, clonazepam,
diazepam
First line for severe
anxiety
Sedation, confusion, addiction
potential, avoid alcohol
Ideally on short-​term basis only;
caution in elderly
Calcium current inhibitor
Pregabalin
Second line
Sedation, dizziness
Recently approved for anxiety
in Europe
Table 26.5.8.8  Some examples of when to refer for consultation or treatment
Practitioner
Modalities used
Patient preference for psychotherapy
Psychologist, psychiatrist,
other trained mental health
professional
Cogntive behavioural therapy, trauma-​focused psychotherapy, insight-​oriented
psychotherapy, and others
Severe or refractory symptoms
Psychiatrist
Consultation, pharmacotherapy, psychotherapy
Diagnostic uncertainty
Psychiatrist
Thorough review of history, medical issues
Social anxiety
Psychologist or psychiatrist
Behavioural therapy, medication
Obsessive-​compulsive disorder
Psychologist or psychiatrist
CBT (exposure and response prevention), selective serotonin reuptake inhibitors (SSRIs),
or clomipramine
Simple phobias
Psychologist or psychiatrist
Behavioural therapy (systematic desensitization)

26.5.9 Acute stress disorder, adjustment disorders
26.5.9 Acute stress disorder, adjustment disorders, and post- traumatic stress disorder 6506 Jonathan I. Bisson
SECTION 26  Psychiatric and drug-related disorders
6506
and panic (e.g. sertraline 200 mg daily). CBT for OCD is a specific
modality—​gradual exposure to the feared stimulus such as dirt
paired with relaxation, reframing, and eventual response prevention
(i.e. not permitting hand-​washing). This form of psychotherapy is
not generally within the scope of physicians’ expertise.
Specific phobias such as snake or bridge phobias rarely present in
medical settings, but needle or pill-​swallowing phobias may inter-
fere with medical care. CBT is the preferred modality, and includes
talking about the fears and systematic desensitization, in which the
patient is gradually exposed to the feared stimulus. As with OCD, a
trained therapist usually delivers this.
Outcome
Without treatment, anxiety disorders tend to become chronic. Overall,
approximately half of patients with anxiety disorders respond fully to
either drug or psychological treatment and the remainder respond to
varying degrees, but the relapse rate is high. Drug treatment should
then be continued for a further 12 months and there should be follow
up with maintenance therapy after treatment with CBT.
FURTHER READING
Craske MG, Stein MB (2016). Anxiety. Lancet, 388, 3048–​59.
Kroenke K, et al. (2010). The patient health questionnaire somatic,
anxiety, and depressive symptom scales: a systematic review. Gen
Hosp Psychiatry, 32, 345–​59.
National Institute of Health and Care Excellence (NICE) (2014).
Anxiety disorders. Quality standard [QS53]. https://​www.nice.org.
uk/​guidance/​qs53
Roy-​Byrne PD, et al. (2008). Anxiety disorders and comorbid medical
illness. Gen Hosp Psychiatry, 30, 208–​25.
26.5.9  Acute stress disorder,
adjustment disorders, and
post-​traumatic stress disorder
Jonathan I. Bisson
ESSENTIALS
Acute stress disorder, adjustment disorders, and post-​traumatic stress
disorder are all psychiatric consequences of traumatic experiences.
Because trauma is so common in medical practice, in the form of
accidents, severe illness, and sometimes medical and surgical treat-
ments, these disorders are commonly seen by physicians. An initial
severe reaction to a traumatic event such as severe accident is an
acute stress disorder and is commonly characterized by dissociation.
A more long-​lasting emotional reaction to ongoing stress such as a
new diagnosis of life-​threatening illness is termed an adjustment dis-
order. An often longer-​lasting and more severe psychological reaction
associated with repeated mental re-​experiencing of the traumatic
event is called post-​traumatic stress disorder. These trauma-​related
disorders are not only an important cause of suffering but may also
complicate medical care, hence they require recognition and appro-
priate treatment.
Introduction
There is a group of psychiatric disorders specifically defined as being
a response to severe psychological stress or trauma. These trauma-​
and stressor-​related disorders include acute stress disorder, adjust-
ment disorders, and post-​traumatic stress disorder (PTSD). Acute
stress disorder is the immediate emotional and behaviour reaction
to an acute stress, for example, being told that a family member has
died unexpectedly. Adjustment disorders are longer-​lasting emo-
tional and behavioural reactions to ongoing stressors, such as a new
diagnosis of cancer. Post-​traumatic stress disorder (PTSD) is usually
a longer-lasting and severer effect of trauma, and is associated with
the traumatic event being involuntarily relived in the imagination.
These disorders are common in medical practice. Accidents and
acute illness may be traumatic, as on occasion may treatment itself.
These disorders are not only an important cause of suffering but may
also significantly complicate medical care, for example, by leading to
the avoidance of essential medical treatment.
Aetiology
Trauma generally refers to an event that is, or is perceived to be,
severe enough to pose a threat to one’s own or another person’s
physical or psychological integrity. Consequently many hospital-
ized patients may be considered to have suffered trauma, but most
people exposed to traumatic events do not go on to develop a mental
disorder; they are surprisingly resilient in the face of adversity.
However, many people who have suffered traumatic events become
severely distressed and some go on to develop a mental disorder. The
criteria for trauma associated with acute stress disorder and PTSD
are shown in Box 26.5.9.1.
Epidemiology
The point prevalence of acute stress disorder following exposure
to traumatic events is between 5 and 20%, depending on the type
Box 26.5.9.1  DSM-​5 acute stress disorder/​PTSD qualifying
traumatic event criteria
Exposure to actual or threatened death, serious injury, or sexual violence
through:
•	 Direct experience
•	 Witnessing, in person
•	 Learning of event happening to a close family member or friend
(actual or threatened death must be violent or accidental)
•	 Repeated or extreme exposure to aversive stimuli (e.g. human remains
collection, police, and details of child abuse)
26.5.9  Acute stress disorder, adjustment disorders, and post-traumatic stress disorder
6507
of trauma and its severity. The point prevalence of adjustment dis-
orders in the general population is between 3 and 12%, with a much
higher prevalence in medical populations. The 12-​month preva-
lence of PTSD is around 3%. Some traumatic events are more likely
to precipitate PTSD than others; for example, the rate is over 50%
after rape, 15% in conflict-​affected populations, and 7.5% following
accidents.
Clinical features
The key clinical feature of these disorders is a significant psycho-
logical reaction to a traumatic event.
Acute stress disorder
This is an immediate response to a severe stressor. A person with
acute stress disorder typically reports experiencing the world
as unreal or dreamlike, feeling detached from their body, or that
they are having increasing difficulty recalling specific details of the
traumatic event (dissociative amnesia). The traumatic event may
be persistently re-​experienced as recurrent images, thoughts, or
dreams. There may also be avoidance of stimuli that arouse recol-
lections of the trauma (e.g. avoiding thoughts, feelings, conver-
sations, activities, places, and people). They may also suffer from
anxiety or symptoms associated with increased arousal such as dif-
ficulty sleeping, irritability, and poor concentration.
The symptoms of acute stress disorder must last for a minimum
of three days and a maximum of four weeks, and must occur within
four weeks of the traumatic event. The person may cope with their
emotional reaction by misuse of drugs or alcohol, which complicates
the clinical picture.
Adjustment disorders
These disorders are a longer-​term response to ongoing stressors
of a range of severities. The symptoms of adjustment disorders
are varied and often include low mood, anger, anxiety, and sleep
disturbance. These symptoms must be out of proportion to the
severity or intensity of the stressor and be associated with signifi-
cant impairment in social, occupational, or other important areas
of functioning. They occur within three months of the onset of
the stressor(s) and do not last for longer than six months after the
stressor and its consequences have ended. The person does not
meet the criteria for another form of mental disorder. Prolonged
adjustment disorders can occur, for example, in individuals ex-
periencing enduring stressors such as chronic physical illness
or pain.
Post-​traumatic stress disorder
This a more severe disorder following exposure to severe
trauma. The symptoms of post-​traumatic stress disorder (PTSD)
are summarized in Table 26.5.9.1. In addition to the qualifying
traumatic event, additional symptoms (one or more intrusion
symptoms, one, or both avoidance symptoms, two or more nega-
tive alterations in cognitions and mood, and two or more al-
terations in arousal and reactivity) with a duration of at least
one month and clinically significant distress or functional im-
pairment are required to make the diagnosis. Symptoms usually
commence shortly after the traumatic event, but there may be
delayed onset if the full diagnostic criteria are not met within
the first six months.
Assessment and differential diagnosis
In assessing individuals, the main differential diagnosis to consider
is a normal reaction to a traumatic event. Distress can be a normal,
healthy reaction following a stressful event and it is factors such as
the intensity and duration of symptoms along with impact on func-
tioning that are important to consider in determining whether a
reaction is pathological or not. These conditions must also be dif-
ferentiated from other psychiatric diagnoses including depressive
disorders and anxiety disorders.
Acute stress reactions are defined as occurring within one month
of a trauma. Adjustment disorder is defined as symptoms that do not
last longer than six months after the stressor and its consequences
have ended. Prolonged adjustment disorders can occur, for example,
in individuals experiencing enduring stressors such as chronic phys-
ical illness or pain. Comorbid psychiatric diagnoses are common,
especially with PTSD; the commonest being major depressive dis-
order, panic disorder, other anxiety disorders, and substance abuse
or dependence disorder. These may require treatment in their
own right.
Table 26.5.9.1  DSM-​5 post-​tramatic stress disorder (PTSD)
symptom criteria
Criteria group
Individual criteria
Intrusion
Recurrent, involuntary, and intrusive distressing memories
Recurrent distressing dreams (content and/​or affect
related)
Dissociative reaction (acting or feeling as if event recurring)
Intense or prolonged psychological distress to cues
Marked physiological reactions to cues
Avoidance
Avoidance or efforts to avoid distressing thoughts or
feelings about or closely associated with the trauma
Avoidance or efforts to avoid external reminders (people,
places, conversations, activities, objects, situations)
Negative
alterations in
cognitions and
mood
Inability to remember an important aspect (typically due
to dissociative amnesia)
Persistent and exaggerated negative beliefs or expectations
about oneself, others, or the world (e.g. ‘I am bad’,
‘No one can be trusted’, ‘The world is completely
dangerous’)
Persistent, distorted cognitions about the cause or
consequences that lead to self-​blame or the blame
of others
Persistent negative emotional state (e.g. fear, horror, anger,
guilt, shame)
Markedly diminished interest or participation in significant
activities
Feelings of detachment or estrangement from others
Persistent inability to experience positive emotions
(e.g. happiness, satisfaction, love)
Marked
alterations in
arousal and
reactivity
Irritable behaviour and angry outbursts (with little or no
provocation)
Reckless or self-​destructive behaviour
Hypervigilance
Exaggerated startle response
Problems with concentration
Sleep disturbance
SECTION 26  Psychiatric and drug-related disorders
6508
Treatment of trauma-​related disorders
Prevention
Primary prevention through reducing exposure to traumatic events
is the optimal approach to prevent these disorders, but is clearly dif-
ficult to deliver. There has been considerable interest in providing
specific early interventions to prevent PTSD. One-​off interventions
provided to everyone involved in a traumatic event such as psycho-
logical debriefing (a structured process of working through the event
in detail, normalizing reactions, and advising individuals of ways to
deal with them) have not been shown to prevent PTSD despite being
widely advocated. In fact, there is some evidence that one-​off inter-
ventions may be harmful to some people, particularly those who are
most distressed after traumatic events. As a result, most contemporary
guidelines advise against this approach and recommend instead the
provision of practical, pragmatic support delivered in an empathic
manner using the principles of psychological first aid (Box 26.5.9.2).
This form of support can be taught to individuals with no previous
training in mental health and is appropriately provided by physicians
and other non-​mental health professionals in general healthcare set-
tings, and it has become increasingly popular and adopted despite the
fact it still has a very limited evidence base to support it.
Early treatment
The lack of evidence for early psychological interventions following
traumatic events has led to approaches that aim to identify those who
remain distressed and at risk of developing an acute stress disorder
or PTSD between two weeks and three months after the traumatic
event. Trauma-​focused cognitive behavioural therapy prevents the
development of more chronic forms of PTSD in such individuals.
There is no evidence to support the routine use of pharmacological
intervention such as antidepressant drugs to prevent or to treat PTSD
within three months of a traumatic event. However, there is some
evidence that giving hydrocortisone shortly after a traumatic event
can reduce the incidence of PTSD in individuals with severe medical
conditions such as septic shock. It is unclear if this finding generalizes
to traumatized individuals who are not severely physically ill.
Drug treatment can have a place in treating severe symptoms such
as insomnia that have not responded to psychological approaches.
Guidelines recommend the use of sedative antidepressants as op-
posed to benzodiazepines in such cases, because the latter may ex-
acerbate symptoms of PTSD.
If an individual is suffering from clinically significant symp-
toms of acute stress disorder or PTSD following a traumatic event
that do not respond to practical, pragmatic support delivered in an
empathic manner using the principles of psychological first aid, it
would be appropriate to consider referral to a service that can pro-
vide the evidence-​based interventions described.
Psychological treatment
There is some evidence that psychological treatment is effective in
the treatment of adjustment disorders. It is also important to help
the patient to address any ongoing stressors, if possible.
Psychological treatments are also effective in the treatment
of PTSD. These are specific therapies which are trauma focused
(such as trauma-​focused cognitive behavioural therapy or eye
movement desensitization and reprocessing; Table 26.5.9.2).
Non​trauma-​focused psychological treatments (e.g. stress man-
agement, psychodynamic therapy) appear to be less effective but
are probably better than nothing. For more complex presentations
of PTSD, it is often argued that individuals may benefit from a
process termed ‘emotional stabilization’ before beginning trauma-​
focused work. This ‘emotional stabilization’ may include help
with basic needs such as physical difficulties and social problems
(e.g. accommodation, food, clothes, money) along with stress
management, skills training in interpersonal relationship and
emotional regulation, and symptom-​relieving drug treatment.
Pharmacological treatment
Selective serotonin reuptake inhibitors are effective in reducing
symptoms of PTSD; the best evidence is for fluoxetine, paroxetine,
and sertraline. The serotonin and noradrenaline inhibitor venlafaxine
is similarly effective. Other drugs, including mirtazapine, amitrip-
tyline, and phenelzine have been found effective in single random-
ized controlled trials that have not been replicated.
Outcome
Acute stress reaction and adjustment disorders tend to resolve over
time, although a severe acute stress disorder may predict the later
Table 26.5.9.2  Evidence-​based trauma-​focused psychological
treatments for PTSD
Trauma-​focused
cognitive behavioural
therapy (TFCBT)
Exposure
–​  The therapist helps the PTSD sufferer to confront
their traumatic memories (written or verbal
narrative, detailed recounting of the traumatic
experience, repetition).
–​  In vivo repeated exposure to avoided and fear-​
evoking situations that are now safe but which are
associated with the trauma.
Cognitive therapy
–​  Focus on the identification and modification of
misinterpretations that lead the PTSD sufferer to
overestimate current threat (fear).
–​  Also focus on modification of beliefs related to
other aspects of the experience and how the
individual interprets their behaviour during the
trauma (eg issues concerning guilt and shame).
Eye movement
desensitization and
reprocessing (EMDR)
Standardized, trauma-​focused procedure with
several elements. These involve the use of bilateral
physical stimulation (eye movements, taps, or tones),
hypothesized to stimulate the individual’s own
information processing in order to help integrate the
targeted event as an adaptive contextualized memory.
Box 26.5.9.2  Components of psychological aid as described
by the Inter-​Agency Standing Committee in 2007
•	 Protection from further harm
•	 Opportunity to talk without pressure
•	 Non​judgemental listening
•	 Identifying and meeting basic practical needs and concerns
•	 Discouraging negative ways of coping
•	 Encouraging normal daily routines and positive coping
•	 Encouraging, but not forcing, company from family or friends
•	 Offering the possibility to return for further support
•	 Referring to local support or clinicians

26.6 Changing unhealthy behaviours 6524 26.6.1 Bri
26.6 Changing unhealthy behaviours 6524 26.6.1 Brief interventions for excessive alcohol consumption 6524 Amy O’Donnell, Eileen Kaner, and Nick Heather
CONTENTS
26.6.1	 Brief interventions for excessive alcohol
consumption   6524
Amy O’Donnell, Eileen Kaner, and Nick Heather
26.6.2	 Obesity and weight management   6529
Susan Jebb and Paul Aveyard
26.6.3	 Smoking cessation   6533
Paul Aveyard
26.6.1  Brief interventions for
excessive alcohol consumption
Amy O’Donnell, Eileen Kaner, and Nick Heather
ESSENTIALS
The treatment and prevention of alcohol-​related harm requires that
attention is paid not only to alcohol dependence, but also to haz-
ardous and harmful drinking. The prevalence of these problems is
high, amounting to about one in four of the adult population of the
United Kingdom. The usual goal of intervention is to reduce drinking
to low-​risk levels, although it may also be abstinence. Screening pa-
tients for alcohol problems and providing brief interventions to those
identified are potentially effective ways of improving patients’ health
and reducing their risk of future harm. The intervention of simple,
structured advice can be delivered without extensive training in 3
to 5 minutes. More intensive brief behavioural counselling requires
training and takes 20 to 30 minutes, often with follow-​up visits.
Introduction
Alcohol is a significant risk to public health. Globally it is the fifth
leading cause of morbidity and premature death after high blood
pressure, tobacco smoking, household air pollution from solid fuels,
and a diet low in fruits.
Excessive alcohol consumption is causally related to over 60 dif-
ferent medical conditions, including liver cirrhosis, cancer, and
cardiovascular disease. There are additional wider social and eco-
nomic consequences which extend beyond the individual drinker to
their families, local communities, and society as a whole.
Alcohol-​related harm is associated with fewer years in formal
education and, ultimately, educational underachievement. In the
workplace, excessive alcohol consumption increases the risk of
unemployment and can lead to disciplinary problems and low
productivity.
Heavy alcohol consumption is also associated with family dis-
ruption, child abuse, and neglect, with homicide, crime, and
drink-​driving fatalities, and is a contributory factor for risky sexual
behaviour, sexually transmitted diseases, and HIV infection.
When those at risk of harm are added to those who have al-
ready incurred it, the number of individuals whose lives may be
adversely affected in some way by their drinking approaches one
in four of the adult population. This is comparable to the number
whose health is directly affected by smoking. It is important to
note that most alcohol-​related problems that occur in a popula-
tion are not due to the most problematic drinkers but to a much
larger group of hazardous and harmful drinkers:  this is known
as the prevention paradox. A prior focus on the concept of alco-
holism has distracted attention from full range of alcohol-​related
problems. Consequently, the scope of treatment and preventive ef-
forts should be broadened to reach all those at risk. Brief interven-
tions in medical practice have a crucial role to play in this strategy
(Fig. 26.6.1.1).
The problem
Excessive drinking
Excessive drinking can be defined as drinking beyond the limits re-
commended by medical authorities. These are based on the level of
consumption identified by epidemiological evidence as the point
where the risk of harm begins to increase. In this respect, there is
a recognized continuum of both alcohol consumption and harm,
meaning that abstinence represents the most effective approach to
minimizing risk. If adults choose to continue to drink, less is better,
and limiting consumption to no more than 20 g of alcohol per day
will keep the lifetime risk of dying from an alcohol-​related condition
to less than one in a hundred.
Currently in the United Kingdom, government guidance is that
adult men and women should not regularly drink more than 14
26.6
Changing unhealthy behaviours
26.6.1  Brief interventions for excessive alcohol consumption
6525
units of alcohol a week on a regular basis (where one unit = 8 g
(10 ml) of pure alcohol), should spread their drinking evenly over
three or more days, and should have several drink-​free days each
week. However, there is a need for clearer, evidence-​based guidelines
for specific population groups, such as younger and older people,
and pregnant women.
Hazardous and harmful drinking
The International Statistical Classification of Diseases and Health-​
related Problems, tenth revision (ICD-​10), defines harmful use
of a psychoactive substance as a pattern of use which is already
causing damage to physical or mental health. Hazardous use is
defined in the World Health Organization’s lexicon of alcohol and
drug terms as a pattern of substance use that increases the risk
of harmful consequences for the user. Thus, hazardous drinking
can be defined as consumption at a level, or in such a pattern, that
increases an individual’s risk of physical or psychological conse-
quence, while harmful drinking is defined by the presence of these
consequences.
Single occasion heavy (‘binge’) drinking
There is a substantially increased risk of short-​term harms (acci-
dents, injuries, and even deaths) faced by people who drink high
levels of alcohol within a single day. The risks of injury have been
found to rise between 2–​5 times when 5–​7 units are drunk in a 3–​
6 hour period. Such high intensity drinking is sometimes called
‘binge drinking’, and binge drinkers may or may not drink on a
regular basis.
The opportunity
Physicians see many people whose presentation is a consequence
of drinking or whose future health is at risk from drinking.
Patients with alcohol problems consult general practitioners
nearly twice as often as others. The most common presentations
are gastrointestinal, hypertensive, psychiatric, and following ac-
cidents. However, it is likely that less than half of these primary
care patients will have their alcohol problem identified. In general
medical and surgical hospital wards, as many as 30% of all male
admissions and 15% of female admissions are excessive drinkers.
Again, few of these patients will be identified as hazardous or
harmful drinkers. Among emergency department attenders, 40%
are excessive drinkers. Alcohol attributable hospital admissions
in the United Kingdom were over 1.22 million in 2011/​12, a 139%
increase since 2002/​03.
Intensive specialist treatment (e.g. detoxification in hospital,
combined with residential rehabilitation)
Treatments and interventions (examples)
Level of alcohol problem
Severely
dependent
Harmful
Hazardous
Not yet developed
Moderately
dependent
THE RANGE OF ALCOHOL TREATMENTS AND INTERVENTIONS
Public health education programmes
NOTES
Not yet developed: people who currently have no level of alcohol misuse.
Hazardous: drinking applies to anyone drinking over the limits recommended by the UK Department of Health.
Harmful: showing clear evidence of alcohol-related problems.
Moderately dependent: Likely to have increased tolerance of alcohol, suffer withdrawal symptoms, and have lost some degree of
control over their drinking.
Severely dependent: may have withdrawal fits (delirium tremens: e.g. confusion or hallucinations usually starting between two or
three days after the last drink); may drink to escape from or avoid these symptoms.
Individual drinkers may move between categories of alcohol problem over time and the boundaries between categories are not
clear-cut. Likewise, the treatments are indicative and may, in some circumstances, be appropriate for the other categories of
alcohol problem.
Source: Adapted from Broadening the Base of Treatment for Alcohol Problems, Institute of Medicine, 1990
Short (5–10 minutes) medical advice (’brief advice’) in
mainstream health or other, nonhealth settings (e.g. by a GP)
An extended period of medical advice (’extended brief
advice’) in mainstream health or other settings
Specialist treatment in generalist or specialist settings
(e.g. detoxification at home, with counselling)
Fig. 26.6.1.1  The range of alcohol treatments and interventions.
National Audit Office. Reducing Alcohol Harm: health services in England for alcohol misuse. London: National Audit Office, 2008.
SECTION 26  Psychiatric and drug-related disorders
6526
Brief interventions aim to detect alcohol problems at an early
stage when they are most amenable to adjustment, and to pro-
mote positive behaviour change, thus avoiding the development
of more serious future problems. Brief intervention assumes that
drinking behaviour results from an interaction between an indi-
vidual, their behaviour, and the social and physical environment.
Thus, drinking behaviour is influenced not only by an individual’s
attitudes towards alcohol, their knowledge about its risks, and their
perceptions of its reinforcing effects, but also by the attitudes of
family members and friends towards drinking, and the patterns
of use within their social group. Brief interventions are ‘oppor-
tunistic’ because they take advantage of medical consultations
whether related to alcohol problems or not. They are normally re-
stricted to excessive drinkers with little or no evidence of alcohol
dependence. Those more seriously impaired are usually referred to
specialist services.
Identifying hazardous and harmful drinkers
Screening is the process used to identify patients whose alcohol con-
sumption places them at increased risk of physical or psychological
complications, and who might benefit from a brief preventive inter-
vention. Laboratory tests are one way of screening. Tests that may be
abnormal include the mean corpuscular volume (MCV), γ-​glutamyl
transferase (GGT), carbohydrate-​deficient transferrin (CDT),
and the ratio of alanine aminotransferase (ALT) to asparatate
aminotransferase (AST). However, standardized questionnaires
have better sensitivity and specificity than laboratory indicators,
particularly in terms of their ability to successfully identify exces-
sive yet non​dependent drinkers. In addition, questionnaire-​based
screening is less costly than laboratory analysis, is far less intrusive,
and is more acceptable to patients.
The alcohol use disorders identification test (AUDIT) was the first
standardized instrument designed specifically by the World Health
Organization to detect hazardous and harmful drinking in primary
healthcare. AUDIT is a 10-​item questionnaire that includes items
on drinking frequency, quantity, and intensity (heavy drinking
episodes), together with experience of alcohol-​related problems
and dependence (Fig. 26.6.1.2). At an indicative score of 8+ out
of a possible 40, the ability of AUDIT to detect genuine excessive
drinkers (sensitivity) and to exclude false cases (specificity) is 92%
and 93%, respectively.
Although relatively brief with only 10 items, the full AUDIT might
be considered too lengthy for use in routine practice, especially if
screening is carried out during the consultation. For this reason,
shorter versions of the AUDIT have been developed, including the
following:
•	 AUDIT-​C—​the first three (consumption) items of the AUDIT.
A score of 5+ indicates hazardous or harmful drinking.
•	 Fast alcohol screening test (FAST)—​a two-​stage screening pro-
cedure based on four of the AUDIT items. Item 3 is asked first
and classifies over half of respondents as either non​hazardous
(Never) or hazardous (Weekly/​Daily or almost daily). Only those
not classified at the first stage (those responding Less than
monthly/​Monthly) go on to the second stage which consists of
AUDIT items 5, 8, and 10 (see Fig. 26.6.1.2). A response other
than ‘never’ to any of these three items classifies the respondent as
a hazardous drinker.
•	 Single alcohol screening questionnaire (SASQ): ‘When was the
last time you had more than ‘x’ drinks in one day?’ (where x = five
for men and four for women (United States values), eight for men,
and six for women (UK values)). Possible responses are: never;
over 12 months; 3–​12 months; within 3 months. The last response
suggests hazardous or harmful drinking.
These shorter scales are quicker to administer but less accurate.
They are therefore recommended as a pre-​screening procedure to
quickly filter out negative cases, leaving the full AUDIT questions
to the smaller pool of cases to provide an accurate and differential
assessment of alcohol-​related risk or harm.
There is debate about whether all patients attending medical
clinics should be screened or only predefined groups. The latter
might include new patient registrations in general practice, special
types of clinic or ward where hazardous and harmful drinkers are
more likely to be found, and emergency department services for
presentations associated with hazardous or harmful drinking. The
National Institute for Health and Clinical Excellence (NICE) re-
commends that screening should be a routine part of practice but
that, where universal screening is not practicable, it should focus on
patients at increased risk of harm from alcohol and those with an
alcohol-​related condition.
Intervening to help patients reduce their intake
Interventions aim to help the patient reduce consumption or abstain
before seriously adverse consequences arise, and before alcohol de-
pendence and problems have reached levels that make treatment
difficult.
Brief interventions can be effective in helping patients reduce
their alcohol consumption. The evidence is particularly strong
in primary care, where the ‘number needed to treat’ (NNT: the
number of hazardous or harmful drinkers that need to receive a
brief intervention for one to reduce drinking to low-​risk levels) is
about 10. The effectiveness of brief alcohol intervention in emer-
gency care, general hospital, obstetric or antenatal care, social
care and educational, and/​or community settings shows less
consistent benefit, but this may reflect a lack of evidence rather
than lack of efficacy in these settings. It seems unlikely that an
intervention that is effective in primary would not work in sec-
ondary care, if delivered well. However, it is important to note
that substantial reductions, even though short of reaching low-​
risk drinking, are also a valuable contribution to individual and
public health.
While brief interventions vary in length, content, and theor-
etical orientation, two basic forms of intervention may be de-
scribed:  simple brief advice (brief, structured intervention) and
extended brief intervention (brief behavioural counselling). These
two forms of brief intervention are included in the NICE guidance
on the prevention of harmful and hazardous drinking.
Simple brief advice
This consists of simple advice to cut down or abstain from drinking.
The advice is personalized to take into account the particular
26.6.1  Brief interventions for excessive alcohol consumption
6527
circumstances of the individual patient and their level of consump-
tion in relation to population norms for their sex, and to appeal
to any specific alcohol-​related difficulties they may recognize as
applying to them. These may include social and psychological dif-
ficulties as well as medical problems. The delivery of simple brief
interventions should, as far as possible, follow the principles de-
scribed by the acronym FRAMES:
•	 structured and personalized feedback on risk and harm
•	 emphasis on the patient’s personal responsibility for change
AUDIT
Scoring system
Your
score
0
1
2
3
4
How often do you have a drink containing
alcohol?
Never
Monthly
or less
2–4
times per
month
2–3
times
per week
4+
times
per week
How many units of alcohol do you drink on a
typical day when you are drinking?
1–2
3–4
5–6
7–9
10+
How often have you had 6 or more units if
female, or 8 or more if male, on a single
occasion in the last year ?
Never
Less
than
monthly
Monthly
Weekly
Daily or
almost
daily
Daily or
almost
daily
Daily or
almost
daily
Daily or
almost
daily
Daily or
almost
daily
Daily or
almost
daily
How often during the last year have you found
that you were not able to stop drinking once you
had started?
Never
Monthly
Weekly
How often during the last year have you failed to
do what was normally expected from you
because of your drinking?
Never
Monthly
Weekly
How often during the last year have you needed
an alcoholic drink in the morning to get yourself
going after a heavy drinking session?
Never
Monthly
Weekly
How often during the last year have you had a
feeling of guilt or remorse after drinking?
Never
Monthly
Weekly
How often during the last year have you been
unable to remember what happened the night
before because you had been drinking?
Never
Monthly
Weekly
Have you or somebody else been injured as a
result of your drinking?
No
Yes,
but not
in the
last year
Yes,
but not
in the
last year
Yes,
during
the last
year
Yes,
during
the last
year
Has a relative or friend, doctor or other health
worker been concerned about your drinking or
suggested that you cut down?
No
Scoring: 0–7 Lower risk, 8–15 Increasing risk,
16–19 Higher risk, 20+ Possible dependence
SCORE
This is one unit
of alcohol…
Half pint of
regular beer,
lager, or cider
1 small glass
of wine
Pint of regular
beer/lager/
cider
2
3
1.5
440 ml
440 ml
4
2
2
9
Pint of premium
beer/lager/
cider
Alcopop or
can/bottle of
regular lager
Can or premium
lager
or strong beer
Can of super
strength
lager
Glass of wine
(1.75 ml)
Bottle of
wine
1 small
glass of
sherry
1 single
measure
of aperitifs
1 single
measure
of spirits
…and each of
these is more
than one unit
Less
than
monthly
Less
than
monthly
Less
than
monthly
Less
than
monthly
Less
than
monthly
Fig. 26.6.1.2  The AUDIT screening questionnaire.
Scoring: 0—​7 Lower risk, 8—​15 Hazardous, 16—​19 Harmful, 20+ Possible dependence.
From Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M (1993). Development of the Alcohol Use Disorders Identification
Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption-​II. Addiction 88: 791−804.
SECTION 26  Psychiatric and drug-related disorders
6528
•	 clear advice to the patient to make a change in drinking
•	 a menu of alternative strategies for making a change in behaviour
•	 delivered in an empathic and non​judgemental fashion
•	 increase the patient’s confidence in being able to change;
self-​efficacy
Advice can be supported by self-​help material and a follow-​up ap-
pointment to check on progress. Repeat GGT readings or other
laboratory markers of alcohol consumption can be a powerful mo-
tivator. All this can be accomplished in a 5–​10 minute consultation.
Specially developed brief intervention packages are available. One
such package is the SIPS (Alcohol Screening and Brief Intervention
Pilots) Brief Advice Tool, available online (https://​www.sips.iop.kcl.
ac.uk). Only one or two sessions of didactic and experiential training
are needed.
Simple brief advice should be offered to patients who score be-
tween 8 and 15 on the full AUDIT and those whom the practitioner
suspects on other grounds of drinking in a hazardous fashion. It
should also be offered as a minimum to patients who are thought
to need more intensive intervention but who decline it. Ideally, the
delivery of this brief advice should be immediately after a patient has
been screened, otherwise an appointment should be offered as soon
as possible thereafter.
Extended brief intervention
An extended brief intervention typically takes 20–​30 minutes to
deliver and can involve up to four additional sessions. It is often a
condensed form of ‘motivational interviewing’ which aims to elicit,
rather than impose, an increase in motivation to change behaviour.
The level of training required to carry out this form of brief interven-
tion effectively is substantially greater than that for simple advice,
and should involve an emphasis on experiential learning. Again,
further information, guidance, and training materials are avail-
able from the SIPS website (SIPS Brief Lifestyle Counselling Tool).
Clinical guidelines on brief interventions and training materials are
also available from the Primary Healthcare European Project on
Alcohol (http://​www.phepa.net).
Extended brief intervention should ideally be offered to individ-
uals who are showing symptoms of physical or psychological harm
due to their drinking (indicative AUDIT range 16–​19). It may also
be suitable for hazardous drinkers who are ambivalent about their
drinking and wish to discuss it with a healthcare professional, or for
those who have not responded to simple advice and want further
assistance in reducing drinking to lower risk levels. Extended brief
intervention is suitable for use by practitioners (medical, nursing, or
others) with a special interest in alcohol-​related problems.
Electronic brief interventions
Electronic screening and brief interventions, delivered via com-
puter, the internet, and mobile phones, are another way of dealing
with excessive drinking. Electronic interventions include some of
the same features as face-​to-​face interventions (e.g. personalized
feedback, engaging the participant in creating coping strategies,
and goal-​based plans) to motivate the participant to reduce their
alcohol consumption over time. For some people the security,
flexibility and anonymity of this approach is more acceptable than
traditional (face-​to-​face) methods. For practitioners, they provide a
means of avoiding the need to engage their patients in a discussion
about alcohol and offer an acceptable and cost-​effective alternative.
Evidence on electronic brief interventions is encouraging, sug-
gesting they can reduce weekly drinking by around three standard
(UK) drinks per week. However given these effects are generally
short term, electronic interventions may be most appropriate when
used either as an adjunct to face-to-face advice delivered by practi-
tioners, or for those who are unlikely to visit their doctor or nurse.
Patients with possible dependence
Patients who score 20 or above on the full AUDIT should be re-
ferred to a specialist services for assessment of an alcohol depend-
ence syndrome. Some recent research has reported promising
findings on the effectiveness of extended brief interventions among
patients with alcohol dependence identified in emergency depart-
ments and general hospital wards who would otherwise be unlikely
to receive any kind of help. There is a clear need to better integrate
programmes to reduce excessive and dependent drinking into gen-
eral medical care.
Prognosis
For lifestyle interventions, this is best thought of as the likely length of
any intervention effect. Meta-​analysis conducted as part of the 2018
Cochrane review of alcohol interventions in primary care  found that
brief intervention reduced the quantity of alcohol drunk by an average
20 g per week at one year following intervention compared to usual
care. Other positive outcomes include a reduction in alcohol-​related
problems, healthcare utilization, and mortality outcomes. Most trials
report 12-​month outcomes, at which time effect sizes are small but
consistently positive. Positive effects have also been reported up to
48 months, but there is limited information on longer-​term outcomes.
More research on this is needed, including the role of booster sessions
in maintaining or reinstating reductions in drinking.
FURTHER READING
Babor TF, et al. (2001). AUDIT: The alcohol use disorders identification
test. Guidelines for use in primary care, 2nd edition. World Health
Organization, Geneva.
Kaner EFS, et al. (2017). Personalised digital interventions for redu-
cing hazardous and harmful alcohol consumption in community-
dwelling populations. Cochrane Database Syst Rev, (9), CD011479.
Kaner EFS, et al. (2018). Effectiveness of brief alcohol interventions in
primary care populations. Cochrane Database Syst Rev, (2), CD004148.
National Institute for Health and Clinical Excellence (NICE) (2010).
Alcohol use disorders:  preventing the development of hazardous
and harmful drinking. NICE Public Health Guidance [PH24].
NICE, London. http://​www.nice.org.uk/​guidance/​PH24
O’Donnell A, et al. (2014). The impact of brief alcohol interventions in
primary healthcare: A systematic review of reviews. Alcohol Alcohol,
49, 66–​78.
Rollnick S, Miller W, Butler C (2008). Motivational interviewing in
health care: Helping patients change. Guilford Press, New York.

26.6.2 Obesity and weight management 6529 Susan Je
26.6.2 Obesity and weight management 6529 Susan Jebb and Paul Aveyard
26.6.2  Obesity and weight management
6529
26.6.2  Obesity and weight
management
Susan Jebb and Paul Aveyard
ESSENTIALS
Obesity is a major public health issue. It is common and a strong risk
factor for many medical conditions, including Type 2 diabetes mellitus,
heart disease, and cancer. Obesity results from an energy intake that
exceeds energy expenditure. Cheap, readily available, energy-​dense
food and sugary drinks together with a sedentary lifestyle are fuelling
the rise in obesity. There is growing evidence that interventions to aid
weight loss are effective in reducing the risk to health associated with
being obese, especially if they combine change in both diet and phys-
ical activity. There is only a limited role for drug treatment of obesity
in routine care. For individuals at the highest risk of comorbid condi-
tions, bariatric surgery is an appropriate option.
Introduction
Obesity is a major risk factor for cardiovascular disease, type 2 dia-
betes, and some cancers. Its causes are complex, but there is much
that general physicians can do to help patients to lose weight before
considering referring them to specialist obesity services. Here we
concentrate on the role of the medical practitioner in management
of obesity in non​specialist medical contexts.
What is obesity?
Weight status is usually calculated using the body mass index (BMI;
weight [kg]/​height2 [m]‌). The health consequences of obesity are
specifically related to excess body fat, hence BMI can be a misleading
measure of risk for some individuals with well-​developed muscu-
lature. Specialist tools are available to measure body composition,
including dual energy X-​ray absorptiometery and bioelectrical im-
pedance analysis, but clinical judgement can usually identify those
whose excess weight reflects excess muscle mass rather than fat.
At a population level, the risk of adverse health consequences
increases progressively with increasing BMI in an almost linear
manner from a BMI of more than 22 kg/​m2. The standard defin-
ition of overweight is a BMI greater than 25 kg/​m2 and obesity over
30 kg/​m2.
The cardiometabolic complications of obesity are particularly as-
sociated with the degree of visceral adiposity. This can only be accur-
ately measured using magnetic resonance or computed tomography
imaging techniques, but measurements of waist circumference are
a useful proxy and can be especially helpful to identify people who
are only moderately overweight (BMI 25–​30 kg/​m2) but at increased
risk (Fig. 26.6.2.1).
Once initiated, the progress of a weight management programme
is most easily monitored by weight loss. Assuming protein intake is
adequate, there is no evidence that specific dietary regimens alter
the proportion of weight lost as fat or influence the site of fat loss.
Physical activity can help attenuate losses of lean tissue and, if of
sufficient duration and intensity, may increase the loss of fat from
visceral fat deposits.
Aetiology
Obesity is caused by an excess energy intake relative to energy
needs over a prolonged period. At a population level, an environ-
ment in which food and drink are readily available in large por-
tions at low cost fuels obesity. This availability of food is combined
with social and cultural trends that reduce the energy costs of daily
life; these include a reduction in manual labour, energy saving
gadgets in the home, a rise in car ownership, and an increase in
Men: <94 cm
Women: <80 cm
Men: 94–102 cm
Women: 80–88 cm
Men: >102 cm
Women: >88 cm
No increased risk
No increased risk
No increased risk
Increased risk
Increased risk
Increased risk
Very high risk
Very high risk
Very high risk
Very high risk
High risk
High risk
BMI
Underweight
(Not applicable)
Underweight
(Not applicable)
Underweight
(Not applicable)
Healthy weight
(18.5–24.9 kg/m2)
Overweight
(25–29.9 kg/m2)
Obese
(3034.9 kg/m2)
Very obese
(>40 kg/m2)
Underweight
(<18.5 kg/m2)
Low
High
Very high
Fig. 26.6.2.1  Identifying patients at increased risk of medical morbidity from obesity (NICE).
Source data from Obesity: identification, assessment and management, NICE Guidelines, November 2014.
SECTION 26  Psychiatric and drug-related disorders
6530
the time spent in front of screens. Each kg of excess tissue contains
approximately 7500 kcals, which provides a useful reminder of the
likely rate of weight loss with dieting; a 500 kcal/​d deficit produces
a weight loss of around 0.5 kg per week. However, the basic law
of thermodynamics is not especially helpful in understanding the
causes of obesity for an individual patient as a precise measure of
energy input and output is hard to achieve. Easier to measure are
markers of high energy intake such as high consumption of sugary
drinks or alcohol, regular takeaway foods and large portion sizes
on the one hand, and markers of low output such as a sedentary
occupation, a high level of leisure screen time, or use of a car for
short journeys.
There is a strong heritable component to obesity. Genetic effects
may be manifest through differences in appetite control and energy
intake. Some endocrine disorders also increase the likelihood of
obesity. The Scottish Clinical Guidelines for obesity note that some
drugs can have marked effects on body weight, with increases of a
few kilograms over 12 weeks, including:
•	 atypical antipsychotics, including clozapine
•	 β-adrenergic blockers, particularly propranolol
•	 insulin, when used in the treatment of type 2 diabetes mellitus
•	 lithium
•	 sodium valproate
•	 sulphonylureas,
including
chlorpropamide,
glibenclamide,
glimepiride, and glipizide
•	 thiazolidinediones, including pioglitazone
•	 tricyclic antidepressants, including amitriptyline
For fuller discussion of the aetiology of obesity, see Chapter 11.6.
Health consequences of obesity
Obesity places a mechanical strain on the body, increasing the risk
of musculoskeletal problems and the need for knee and hip replace-
ments. It also exerts metabolic effects on almost every organ system of
the body. It is the principal non​genetic risk factor for the development
of insulin resistance, with a roughly linear increase in risk of type 2
diabetes from a BMI of 22 kg/​m2 upwards (Fig. 26.6.2.2). For women,
a BMI of 30 kg/​m2 confers a 40-​fold risk of developing diabetes relative
to a BMI of 22 kg/​m2. A person who enters adulthood with a BMI of 30
has a lifetime probability of developing diabetes of over 70%.
The increased risk of premature death associated with obesity is
mainly due to its presumed causal connection to cardiovascular dis-
ease. There is a linear association between BMI (as a proxy for body
fat) and mortality from both ischaemic heart disease and stroke.
This association appears to be explained by the curvilinear associ-
ation between raised body fat and higher low-​density lipoprotein
(LDL) and lower high-​density lipoprotein (HDL), and the linear as-
sociation between body fat and blood pressure (Fig. 26.6.2.3).
Obesity increases the risk of most nonsmoking related cancers
through mechanisms primarily relating to the products of adipose
tissue, including raised levels of oestrogen, insulin-like growth fac­
tors, and inflammatory cytokines.
Collectively, the increased incidence of cardiovascular dis-
ease, diabetes and cancer reduce life expectancy by three years for
someone with a BMI of 30–​35 kg/​m2 and by 10 years for someone
with a BMI of 40–​45 kg/​m2. Obesity is also associated with an in-
creased risk of needing social care in older age. This implies that it is
associated with a longer period of ill health prior to death, and this is
one of the costs of obesity to the economy.
100
90
80
70
60
50
40
30
20
10
22.0–22.9
BMI category (kg/m   )
Age-adjusted relative risk of diabetes
23.0–23.9
24.0–24.9
25.0–26.9
27.0–28.9
29.0–30.9
31.0–32.9
33.0–34.9
≥35.0
0
Fig. 26.6.2.2  Body mass index (BMI) and risk of diabetes in women.
Data from Colditz et al. 1995. Ann Intern Med, 122(7): 481–​6.
26.6.2  Obesity and weight management
6531
Epidemiology
Worldwide, obesity has almost doubled since 1980 and today an esti-
mated 600 million people are obese. Although it is more prevalent in
high-​income nations, the rapid rate of increase in low and middle-​
income countries is putting a particular strain on their healthcare
resources. In the United Kingdom over a quarter of adults are obese
(defined as a BMI >30 kg/​m2), and this proportion is even greater
in certain groups. For example, it is higher among women of black
Caribbean, black African, and Pakistani ethnicities, compared
to the other ethnic groups, and is more common in those of low
socioeconomic status. These differences underpin some of the in-
equalities in life expectancy and disease patterns.
Treatment
Behavioural weight management programmes
Most overweight people who present to general medical services do
not receive any support to reduce weight. The reasons for this in-
clude sensitivities in raising the issue, patchy provision of services,
and lack of confidence in the effectiveness of interventions.
Clinical guidelines in most countries identify a series of steps in
an obesity care pathway (Fig. 26.6.2.4, recognizing that these dif-
ferent steps need to operate as a coherent whole.
There is emerging evidence that a simple prompt by a doctor can
stimulate effective self-​management of obesity. A systematic review of
self-​help interventions found that many are effective, at least in the short
term. Signposting patients to the 12-​week online behavioural weight loss
programme offered by NHS Choices represents a minimal cost option.
Most behavioural programmes are based on dietary change. The
most effective, especially in the medium to long term (more than
one year), are those that also incorporate support for increased
physical activity. There is little evidence to suggest that diets with a
specific macronutrient composition (e.g. low fat, low carbohydrate,
or high protein), are associated with greater long-​term weight loss.
Early differences in weight loss relate to differences in adherence,
suggesting that diet should be tailored to personal preferences and
circumstances.
There is no evidence that exercise-​only programmes are effective
for weight loss.
A review of weight loss interventions specifically suitable for use
in a general medical context found that support provided by a non-​
specialist healthcare professional was ineffective. However, for
people seeking help to lose weight, referral to a community-​based
open-​group weight loss programme, such as WeightWatchers or
Slimming World, led to a mean weight loss of approximately 2.5 kg
at one year. The largest study to directly compare these two ap-
proaches found weight losses of -​1.77 kg and -​4.06 kg, respectively,
in those referred to a practice nurse or a commercial provider
(Fig. 26.6.2.5).
Many areas of the United Kingdom now offer referral programmes
funded by the NHS. Patients welcome the greater frequency of con-
tact with a community group and perceive these groups as more
motivating than the information-​based approach usually offered in
primary care. A recent trial has shown that a brief intervention by
a health professional offering referral to these weight loss services
leads to significantly greater weight loss at one year than advice only.
This represents a cost-​effective first-​line option for people who are
overweight or obese and, if offered routinely, could reduce the popu-
lation prevalence of obesity and comorbid conditions.
Very low energy diets
There is evidence that very low energy diets, providing less than
800 kcals/​d, in combination with a behavioural programme achieve
160
5
4
3
2
1
0
140
120
100
80
15
25
35
50
15
25
35
50
Diastolic
Systolic
Blood pressure
Baseline BMI (kg/m2)
Adjusted for age, smoking, and study
Cholesterol
Blood pressure, cholesterol and BMI
F
F
F
F
F
M
M
M
M
Non-HDL-C
Ratio of means
(non-HDL-C/HDL-C)
HDL-C
M
mm Hg
mmol/litre (or ratio)
Fig. 26.6.2.3  Relationship between BMI and blood pressure or cholesterol.
Reprinted with permission from Elsevier (The Lancet, 2009; 373: 1083−96).
SECTION 26  Psychiatric and drug-related disorders
6532
more than 4 kg greater weight loss at one year than a behavioural
programme alone. At present, the National Institute for Health and
Care Excellence (NICE) recommends these only for patients who
would benefit from acute weight loss, for example, ahead of knee
surgery or fertility treatment, because of concerns that they may be
associated with later rapid weight gain. However, there is no good
evidence that this concern is justified, and recent trials show they are
safe, acceptable and effective in routine care.
Cognitive behaviour therapy
Specialist medical weight management services will sometimes
include interventions using cognitive behavioural therapy, but
there are few high quality trials of this approach and there is little
evidence of effectiveness. In a subgroup of obese people identified
as having binge eating disorder, cognitive behavioural therapy
can reduce the symptoms of binge eating, but is ineffective for
weight loss.
Drug treatments for obesity
There has been limited success in developing drugs to treat obesity
and no centrally acting compounds are licensed for the treatment
of obesity in the United Kingdom. Orlistat, a gastrointestinal lipase
inhibitor, reduces the absorption of dietary fat by approximately
30%. It is essential that patients using this follow a low fat diet in
order to avoid adverse gastrointestinal side effects (steatorrhoea),
and this dietary change is likely to account for as much as 50% of
the observed weight loss. Patients who fail to make dietary changes
will usually experience adverse events, leading to poor medication
adherence and minimal weight loss. Others can be successfully
maintained on orlistat for periods of one year or more with clin-
ically significant weight loss. In a trial over four years, people with
impaired glucose tolerance randomized to receive orlistat plus be-
havioural support lost 6 kg compared to a group receiving similar
behavioural support plus placebo treatment, who lost only 3 kg.
This greater weight loss was associated with a 37% reduction in the
incidence of diabetes. Orlistat is also available from pharmacists in
a reduced (half) dose with proportionally lower rates of weight loss,
but substantially fewer adverse effects.
For patients with impaired glucose tolerance, metformin can
be prescribed. Indirect comparisons suggest that the reduction in
weight appears smaller than with orlistat but the reduction in the
incidence of diabetes is comparable. New injectables used in patients
with diabetes, such as liraglutide, are also associated with significant
weight loss but are not appropriate for routine treatment of obesity.
Surgery
NICE recommends that patients who have a BMI greater than 35 kg/​m2
with obesity-​related comorbidities, or those who are severely obese
Specialiist
MDT services
for severe &
complex obesity,
including bariatric surgery
Primary care specialist services,
including pharmacotherapy and
referral to dietitian
Community/primary care behavioural weight
management services
Primary prevention e.g. workplace interventions, active
travel, food skill training, mass media information and advice
Fig. 26.6.2.4  Outline obesity care pathway.
88
–1.59 kg
–4.03 kg
P < 0.001
86
84
82
80
78
Baseline
2
4
6
9
12
Treatment duration (months)
Body weight (kg)
weight Watchers
Standard care
Fig. 26.6.2.5  Treating obesity in primary care: practice nurse vs. referral
to commercial provider (n = 772).
Jebb et al. 2011. Lancet, 378, 9801: 1485–1492.

26.6.3 Smoking cessation 6533 Paul Aveyard
26.6.3 Smoking cessation 6533 Paul Aveyard
26.6.3  Smoking cessation
6533
with a BMI greater than 40 kg/​m2, may be referred for specialist
review and considered for bariatric services. Several different
surgical techniques are available, with losses ranging from 10 to
15 kg for gastric bands to over 20 kg for gastric bypass with corres-
pondingly greater improvements in health. Long-​term follow-​up
of matched populations shows significant reductions in the inci-
dence of diabetes, myocardial infarction, and stroke, and in overall
mortality rates.
Prognosis
Given the linear associations between adiposity and risk of mor-
bidity and mortality, weight loss should proportionally reduce risk
of future ill health. However, there is much less data on the associ-
ation between weight loss and long-​term health outcomes than there
is on the association of excess weight and health risk.
A systematic review of trials examining the association between
change in weight and change in blood pressure reported that each
kilogram lost reduced systolic blood pressure by 1  mm of mer-
cury, although a systematic review and meta-​analysis of studies
with a follow-​up of longer than 12 months found a smaller benefit.
Similarly, a systematic review and meta-​analysis of studies on the
association between weight loss and change in lipids confirmed the
linear association we might expect between reducing weight and re-
ductions in triglycerides, LDL, and total cholesterol and increases
in HDL cholesterol. In patients with type 2 diabetes, weight loss of
about 5 kg is associated with a reduction in fasting blood glucose of
about 0.2 mmol/​litre at 12 months.
The strongest evidence for a causal association between losing
weight and improved health comes from clinical trials. Systematic
reviews of these show that relatively brief weight loss programmes
reduce the incidence of diabetes by half in the following few years,
despite some weight regain. Two trials with long-​term follow-​up
found that the benefit of the weight loss programme persisted to
at least 10 years, even if the weight lost was later regained. Other
studies show weight loss induced symptomatic improvements in
clinical conditions such as sleep apnoea, atrial fibrillation, and non-​
alcoholic fatty liver disease.
While weight regain is common after all interventions, there are
health benefits from even short periods of reduced weight. Moreover,
with each weight loss attempt, a proportion of people will succeed in
making long-​term changes to their eating and activity, a situation
analogous to interventions for smoking cessation.
Conclusions
There is growing evidence that a range of interventions offered to
patients by medical practitioners can achieve at least short-​term
weight loss and clinical benefits. While bariatric surgery may be
the most effective intervention for individuals with very high BMI
and at significant risk of comorbidities, there is a less costly, but
pressing need to provide access as part of routine medical care to
effective weight management services for the large proportion of
the population who are obese. Treating obesity is a cost-​effective
intervention to reduce the burden of a host of comorbid conditions
at a population level.
FURTHER READING
Aveyard P, et al. (2016). Screening and brief intervention for obesity
in primary care: a parallel, two-​arm, randomised trial. Lancet, 388,
2492–​500.
Dietz WH, et  al. (2015). Management of obesity:  improvement of
health-​care training and systems for prevention and care. Lancet,
385, 2521–​33.
Jensen MD, et al. (2014). AHA/​ACC/​TOS guideline for the management
of overweight and obesity in adults: a report of the American College
of Cardiology/​American Heart Association Task Force on Practice
Guidelines and The Obesity Society. J Am Coll Cardiol, 63, 2985–​3023.
Royal College of Physicians (2015). Action on obesity: comprehensive
care for all. https://​www.rcplondon.ac.uk/​sites/​default/​files/​action-​
on-​obesity.pdf
Wormser D, et al. (2011). Separate and combined associations of body-​
mass index and abdominal adiposity with cardiovascular disease: col-
laborative analysis of 58 prospective studies. Lancet, 377, 1085–​95.
26.6.3  Smoking cessation
Paul Aveyard
ESSENTIALS
Smoking is harmful to health. The main harms are cardiovascular dis-
ease, lung cancer, and chronic obstructive pulmonary disease. Most
people who smoke start in their teens, and some become addicted.
Stopping smoking may be prompted by public policy or price rises,
and while physicians have a role in lobbying for these, the main op-
portunity a physician has to help their patients stop smoking is during
the medical consultation. Advising the patient to stop has some effect,
but is more likely to be effective when combined with practical help,
the best form of which is regular face-​to-​face meetings to support the
patient combined with drugs that reduce craving. Helping a patient
to stop smoking greatly reduces their risk of illness and early death.
Introduction
Tobacco smoking is the world’s leading cause of drug-​related
harm. The rise and fall of smoking in a population can been seen as
occurring in four stages: in stage one the rate of smoking is low and
confined to men, with correspondingly low morbidity and mortality.
In the second stage, the rate rises rapidly among men and starts
among women. By the third stage, the rate rises rapidly in women
and morbidity and mortality become evident. In the fourth stage,
there is a legacy of tobacco-​related harm, which drives tobacco con-
trol, which reduces the rate of smoking. Countries like the United
Kingdom are in the fourth of these stages, with rates of smoking now
falling rapidly; in 2016, only 17% of adults and 3% of young people
smoke. However, smoking remains a major public health problem.
Most patients and all doctors know that smoking is harmful and that
stopping smoking is a good thing. This chapter reviews evidence for
SECTION 26  Psychiatric and drug-related disorders
6534
benefits of stopping smoking and outlines how doctors can inter-
vene most effectively to help their patients to do this.
Smoking behaviour
Initiation of smoking
Most people start smoking in adolescence. This observation is often
ascribed to peer pressure, and there is strong evidence that a person
is more likely to smoke if they are part of a social network in which
others smoke. It is doubtful that the influence is directly due to pres-
sure from a proselytizing minority of smokers systematically re-
cruiting into its ranks; indeed, there is evidence that pressure works
the other way, with young people who start smoking being pres-
surized to desist by their non​smoking peers. Nevertheless, there is
clear evidence that smoking starts as an act of social affiliation with
a strong social meaning in adolescence.
Tobacco addiction
In many countries, most people have tried smoking cigarettes but only
a few people persist. There is strong evidence from twin and adoption
studies that what determines who continues to smoke is explained gen-
etically, as with other drugs of addiction. Furthermore, the propensity
to successfully stop smoking also appears to be explained genetically.
Although candidate genes are associated with smoking persistence,
their individual effects are weak, implying that complex polygenetic
mechanisms are responsible for this unfortunate inheritance.
Smoking is largely maintained by addiction. Most people who
smoke and live in countries where smoking is stigmatized show
signs of dependence. Nicotine is the principal vehicle of addiction
to cigarettes, though nicotine is not particularly liable to cause de-
pendence without being associated with other aspects of smoking
behaviour. These may be regarded as secondary reinforcers and in-
clude the ‘catch’ of smoke in the throat. This may be why few people
become addicted to nicotine without having smoked cigarettes.
The volatile components of cigarette smoke carry the nicotine into
the lungs where it is absorbed in the alveoli and rapidly transported
to the brain. Here it binds to acetylcholine receptors in the ventral
tegmental area. These neurons project to the nucleus accumbens
where they lead to dopamine release in the core and shell, inducing
pleasure and habit-​related learning. Regular smoking leads to
neuroadaptation of this pathway, which helps maintain the behav-
iour. Nicotine is rapidly metabolized by the liver to non​psychoactive
compounds. Consequently, regular smokers come to experience a
nicotine hunger when they have not smoked for a while, creating
a drive to smoke. In addition, nicotine withdrawal induces a mild to
moderate aversive state of negative affect and irritability.
The culmination of these mechanisms is that people who smoke
typically experience unwilled impulses to smoke in situations where
they characteristically smoked in the past. When a person decides
to stop smoking, these impulses are experienced as cravings. The
strength and frequency of cravings decreases over about six weeks,
but this period varies greatly. The aim of smoking cessation treat-
ment is to drive down the strength of urges to smoke and to support
people’s commitment and ability to resist them. The learnt response
to cues that give rise to the urge to smoke are unlearnt as long as
smoking is not reinstated. Maintaining abstinence then becomes
easier. Consequently, the critical period in which smokers need sup-
port not to return to smoking is the first few months of abstinence.
Risks of continued smoking and benefits
of cessation
Smoking remains a highly dangerous behaviour. A  lifetime of
smoking reduces average life expectancy by 10 years. People who
smoke have approximately double the risk of death at any given
age and there is a dose-​response relationship with amount smoked.
Smoking causes this excess morbidity and mortality by three main
routes. These are, in order of importance, cardiovascular disease
(CVD) (principally ischaemic heart disease and stroke), lung cancer,
and chronic obstructive pulmonary disease (COPD).
•	 The risk of CVD is increased three fold in smokers during middle
age. Importantly, for the risk of CVD, light smoking is almost as
hazardous as heavy smoking. Cessation quickly reduces this risk;
it is halved in the first year and falls to that of a lifelong non​smoker
after 10 years.
•	 The risk of lung cancer has a very steep dose-​response relationship
with amount smoked; it increases risk 20-​fold in heavy smokers.
Stopping smoking at any age reduces the risk of developing lung
cancer.
•	 People who smoke are three to five times more likely to suffer
from COPD. As many as 30% of lifelong smokers will develop
COPD. Stopping smoking reverts the rate of decline of lung func-
tion to that of non​smokers and is the only treatment known to
achieve this.
The net effect of both the cumulative damage from smoking and the
remarkable benefits of cessation mean that we can say that for every
day a person smokes after the age of 35 years that person will lose
six hours of life. This evidence underlines the imperative of stopping
smoking before middle age and how important it is for physicians to
help their patients to do this (Table 26.6.3.1).
Helping people to stop smoking
Public health interventions for smoking cessation
The main reason people stop smoking is concern about the effect
on their health, though in many countries the price of cigarettes
is also a factor. Public policy measures can support cessation by
influencing the acceptability, affordability, and availability of cigar-
ettes, and many countries have enacted tobacco control legislation
Table 26.6.3.1  Years of life gained from stopping smoking
at various ages relative to people who continue smoking
throughout life in the British Doctors Study
Age when stopping smoking
Years of life gained
25–​34 years
10
35–​44 years
9
45–​54 years
6
55–​64 years
3
26.6.3  Smoking cessation
6535
and policies. These measures are described in the world’s first public
health policy document, the World Health Organization (WHO)’s
Framework Convention on Tobacco Control.
•	 While measures such as banning smoking in public places are mainly
intended to protect non​smokers from harm, they also reduce the
perceived acceptability of smoking indoors at home and in general.
•	 Specific tobacco taxes are levied in almost all countries, with many
committed to above inflation price increases. Increasing price is
probably the single most effective prompt for cessation and is par-
ticularly motivating when the price increases create ‘left digit ef-
fects’ (e.g. from £6.xx to £7.xx for a pack of cigarettes).
•	 Warnings on packets, particularly graphic warnings, and the removal
of branding logos from cigarette packs affect people’s perceptions of
the acceptability of smoking and lead to some people stopping.
Governments do not automatically adopt these policies. They come
about only because physicians and others lobby for them, hence
physicians have a key role in advocacy in this area.
Physician-​delivered interventions for smoking cessation
Physicians have a directly therapeutic role in supporting their pa-
tients’ efforts to quit smoking. The first and most direct way of doing
this is to advise patients to stop smoking because of the adverse effects
on their health. Giving this advice has been the cornerstone of guide-
lines on helping people stop, because there is clear evidence from a
meta-​analysis of trials that it is effective in promoting attempts to
quit smoking. However, the same meta-​analysis also found that not
only advising but also offering help to stop smoking was even more
effective. It is therefore best for physicians to offer advice about the
harm resulting from smoking and to offer the patient help to stop.
The help should include both psychological support and drug therapy.
These are effective both alone and together in improving the chance of
successful cessation. Without help, half of all quit attempts fail within
a week and only about 5% of attempts are successful at six months.
Psychological support
Psychological support helps achieve smoking cessation by keeping
people committed to the goal that they have set themselves. It can
also help patients to use strategies to make cessation easier, such as
removing or avoiding the cues that prompt them to smoke. Self-​
help resources, such as booklets, are only modestly more effective
than no support. More intensive support provided without direct
personal contact, such as by automated text messages or via online
self-​help programmes, is also only modestly effective. Many coun-
tries provide quitlines and trials suggest that access to a quitline also
modestly boosts success. However, probably the most effective ways
of providing psychological support for stopping is by regular sched-
uled face-​to-​face meetings, either individually or in groups.
Drugs to aid smoking cessation
The effectiveness of drugs in helping patients achieve cessation
relates directly to the degree to which they suppress the urge to
smoke. Three drugs are in widespread use:  bupropion, nicotine
replacement therapy (NRT), and varenicline. A  network meta-​
analysis of randomized controlled trials shows that the two most
effective pharmacotherapies are varenicline and combination NRT.
Combination NRT means using two forms of NRT together, usually
a nicotine patch for long-​term suppression of urges, together with a
short-​acting form of NRT that suppresses the urge to smoke when
administered acutely. The use of these drugs doubles the chance of
successful cessation.
While all medications have adverse effects, those of smoking ces-
sation medication must be compared with the adverse effects of con-
tinued smoking. The main adverse effects are as follows:
•	 Bupropion causes fits in one in 1000 users, which is the most ser-
ious adverse event. Around 1 in 10 users cease treatment due to
adverse events, principally insomnia, headache, dry mouth, and
gastrointestinal upset.
•	 Nicotine replacement causes irritation at the site of administra-
tion (i.e. skin or mouth irritation).
•	 Varenicline has been associated with psychological disturbance
in case reports but not in controlled studies. It commonly causes
nausea and insomnia. Discontinuation due to adverse events oc-
curs in around 1 in 20 users.
Electronic cigarettes
Electronic cigarettes have become popular in recent years. The few
trials so far published suggest that they function as well as conven-
tional NRT. Undoubtedly the rapid increase in popularity of this ap-
proach is likely to lead to product development, which may increase
the appeal still further and increase the efficacy of these and other al-
ternative nicotine delivery devices. While we clearly lack long-​term
epidemiological data on their continued use, analyses of the vapour
produced suggests there are no particular reasons to be concerned
about the health risks for smokers switching to electronic cigarettes.
Conclusions
Many people who smoke try and fail to stop smoking. However, most will
succeed in the end, and the sooner they do so the greater the chance of
avoiding the harms that result from smoking. Repeated attempts to help
them with advice, ongoing face-​to-​face support, and effective pharma-
cotherapy offer the best opportunities to help them stop and avoid the
harm to their health that would result from continuing to smoke.
FURTHER READING
Mechanisms of addiction to tobacco
West R, Brown J (2013). Theory of addiction, 2nd edition. Addiction
Press, Wiley Blackwell, London.
Assisting cessation
Aveyard P, Raw M (2012). Improving smoking cessation at the indi-
vidual level. Tobacco Control, 21, 252–​7.
Aveyard P, et al. (2012). Brief opportunistic smoking cessation inter-
ventions: a systematic review and meta-​analysis to compare advice
to quit and offer of assistance. Addiction, 107, 1066–​73.
Hartmann-​Boyce J, Aveyard P (2016). Therapeutics: pharmacotherapy
for smoking cessation. BMJ, 352, i571.
Harms from smoking and benefits of smoking cessation
Pirie K, et al. (2013). The 21st century hazards of smoking and benefits
of stopping: a prospective study of one million women in the UK.
Lancet, 381, 133–​41.

Paul Aveyard 26.7 Psychiatry, liaison psychiatry,
Paul Aveyard 26.7 Psychiatry, liaison psychiatry, and psychological medicine 6536 Michael Sharpe
ESSENTIALS
Psychiatry first developed as a separate medical specialty about 150 years
ago when physicians were recruited to staff the new lunatic asylums. It
later embraced psychotherapy and more recently has adopted com-
munity rather than hospital-​based working. The fact that psychiatry re-
mains largely separate from other areas of medicine, together with the
increasing focus on technical procedures in medicine, has led to some-
times inadequate psychiatric care for medical patients. Measures to ad-
dress this shortcoming began 50 years ago with the ad hoc development
of liaison psychiatry teams, providing in-​reach psychiatric services from
mental hospitals to general hospitals. A more recent innovation is to re-
integrate psychiatrists into medical teams as specialists in psychological
medicine to provide joined up medical and psychiatric care.
What is psychiatry?
Psychiatry is the branch of medicine that specializes in the diagnosis
and treatment of those illnesses traditionally considered to be ‘mental’
in nature. While there has been a long history of medical interest in
mental illnesses, psychiatry as a defined medical specialty had its ori-
gins only about 150 years ago. Modern psychiatry is a combination of
two main historical strands. The first was a consequence of the setting
up of lunatic asylums from the early 1800s onwards; physicians were
recruited to work in these new institutions built to serve the severely
mentally ill and came to be regarded as specialists in what was called
‘alienism’. This institution-​based care of the seriously mentally ill was
revolutionized in the 20th century by the discovery of effective drugs
for psychosis and depression; innovations that allowed increased
community care and changed how psychiatrists worked. The second
strand arose from the development of psychotherapy or talking treat-
ments. Physicians have long used talking to their patients as a form of
treatment. However, in the early 20th century Freud, a neurologist,
and others developed more intensive forms of talking therapy called
psychoanalysis. Psychoanalysis become influential in the United States
in the first half of the 20th century, but less so in the United Kingdom.
Psychiatrists and psychologists have since developed many new forms
of talking therapy such as cognitive behaviour therapy, which have
proven to be effective for several conditions such as depression and
have become a major form of treatment in psychiatry.
The establishment of psychiatry as a separate medical specialty
was formalized in the United Kingdom in 1971 by the creation of
the Royal College of Psychiatrists. Modern psychiatrists typically
work in multidisciplinary teams and usually in community settings.
The other professional groups making up the multidisciplinary team
include:
•	 Psychologists—​non​medically trained psychology graduates who
have received clinical training (often as a ‘taught doctorate’).
•	 Psychiatric nurses (often working as community psychiatric
nurses, ‘CPNs’) who have training in mental illness, but often have
little or no training in general nursing.
•	 Members of other disciplines such as occupational therapists,
social workers, and generic ‘mental health workers’ who have vari-
able amounts of training.
Psychiatry and the medically ill
Before the rise of modern technological medicine, most physicians
had to rely on listening and talking with the ill person, observing
their behaviour, and using the doctor–​patient relationship as a
therapeutic tool. In the early 20th century, a small number of phys-
icians in teaching hospitals actively specialized in the psychological
aspects of their patients’ medical illnesses. This area of work called
‘psychological medicine’ did not survive in the United Kingdom as
a specialty for physicians. In Germany, driven in part by a much
stronger emphasis on psychoanalysis, a subspecialty of medicine
called psychosomatic medicine, which is separate from psychiatry,
has survived and prospered to this day.
The formal development of a subspecialty of psychiatry that fo-
cuses specifically on the medically ill is relatively recent. It had its
beginning in the United States in the 1950s and has gradually devel-
oped in the United Kingdom from the 1970s onwards. It originally
went by the name of liaison psychiatry, but is increasingly adopting
the old term of ‘psychological medicine’.
What is liaison psychiatry?
Psychiatric and medical services have remained organisationally
separate in the United Kingdom since the setting up of the asy-
lums. This division was maintained with the establishment of sep-
arate mental health trusts in the UK in the 1990s. Consequently,
26.7
Psychiatry, liaison psychiatry,
and psychological medicine
Michael Sharpe
26.7  Psychiatry and psychological medicine
6537
psychiatric services to the medically ill were conceived of as an out-
reach from mental health services into general hospitals, hence the
term ‘liaison’ which refers to the linking of distinct services.
What do liaison psychiatrists do?
Medicine, despite the huge success in identifying and treating dis-
ease processes, often finds itself ill equipped to deal with patients’
other needs. For example:
•	 Patients who have self-​harmed form a significant proportion of
those presenting to general hospital emergency departments
•	A quarter of patients seen by specialist medical services have
anxiety or depression
•	 As many as half of acute medical inpatients suffer from delirium
or dementia
•	A third of medical outpatients suffer from somatic symptoms
inadequately explained by disease (medically unexplained
symptoms)
To complicate matters further, these conditions—​which are typic-
ally deemed psychiatric rather than medical—​are often inextricably
interwoven with medical conditions. This phenomenon is called
multimorbidity and necessitates that the patient receives joined up
medical and psychiatric care.
Common presentations referred to liaison psychiatry teams, the
diagnoses they commonly make, and the interventions they use, are
shown in Table 26.7.1.1.
How do standard liaison psychiatry services work?
Most liaison psychiatry services work by responding to referrals
from physicians, although some screen medical patients to pro-
actively identify psychiatric problems such as depression or al-
cohol misuse. Liaison psychiatry teams are usually employed by a
mental health provider, but have their accommodation in or near
the general hospital. The composition of the liaison psychiatry
team varies, but usually includes one or more consultants in liaison
psychiatry, trainee psychiatrists, and mental health specialist nurses.
Psychologists also commonly work in general hospitals, often as
clinical or health psychologists, and they often work separately from
the liaison psychiatry services.
How to refer a patient to a liaison psychiatrist
The ease of access to skilled help from a psychiatrist varies consider-
ably between hospitals, and seeking it can sometimes be frustrating.
Hospitals that have a dedicated liaison psychiatry service should
ideally provide easy 24-​hour access. Elsewhere a referral may need
to be made to a general psychiatrist working in the community or in
a psychiatric hospital. The initial response to a routine referral may
be from a nurse or psychiatric trainee; if a consultant opinion is re-
quired, this should be specifically requested. Before making a referral,
it is useful for the physician to consider the following questions:
•	 What exactly is the problem you need help with?
•	 What is the differential psychiatric diagnosis?
•	 What type of help are you requesting, and how quickly do you
need it?
It is important to be aware that, just as many physicians are not con-
fident in psychiatric care, many general psychiatrists are not confi-
dent in managing medical conditions and may need clear guidance
on this aspect of the patient’s care. In addition, it is also important
to remember that specialist psychiatric beds are commonly in very
short supply and largely occupied by patients with severe psychotic
illnesses. Consequently, an apparent lack of willingness to ‘take the
patient away’ is more likely to be a reflection of this limitation in
resource than of unhelpfulness by the psychiatrist.
Psychological medicine
There is a recent trend toward increasing the integration of psychi-
atrists into medical services. This is happening for several reasons:
•	 It is becoming clear that people using medical services very often
have a mental illness that merits treatment in its own right and
which complicates their medical care. This is especially the case
with the increasing number of elderly patients and is an important
aspect of the challenge of multimorbidity.
•	 Patients and policymakers are increasingly demanding more effi-
cient and more integrated care, with ‘parity of esteem’ for mental
and physical illness driving policies that require more attention is
paid to mental illness, including in the medically ill.
•	 Research in neuroscience is increasingly raising questions about
the fundamental rationale for distinguishing some illnesses as
‘mental’ and some as ‘physical’, when mental illness has functional
and sometimes structural correlates in the brain.
A recent innovation is to fully reintegrate psychiatry into the general
hospital by employing psychiatrists (and psychologists) as members of
medical teams. The advantages of this way of working are that psychiat-
rists are more accessible to staff and to patients, have a much greater op-
portunity to support and educate their medical and nursing colleagues
in the management of psychiatric disorder, and use the same protocols
and medical records. The result is that the patients experience seamless
care. This model currently operates successfully at the John Radcliffe
Hospital in Oxford. As it is not a liaison service (which means a link
between two services), but is fully integrated into medicine, it is called
an integrated psychological medicine service. The trend towards hope-
fully integrating mental and physical care is likely to gather pace and
will bring psychiatry and medicine back together, to the benefit of both.
Table 26.7.1.1  What do liaison psychiatrists do?
Assess and manage
presentations such as
Make psychiatric
diagnoses such as
Provide interventions
that may include
Anxiety
Confusion
Delusions and
hallucinations
Disturbed behaviour
Low mood
Medically unexplained
symptoms
Non​adherence to
medical treatment
Self-​harm and suicide
risk
Adjustment disorder
Anxiety disorders
Bipolar disorder
Delirium
Dementia
Depressive disorder
Personality disorder
Schizophrenia
Somatic symptom
(somatization)
disorder
Collaborate with and
support medical and
nursing staff
Provide education
Do complex capacity
and Mental Health Act
assessments
Facilitate discharge from
hospital
Link with community
mental health services
Give psychological
treatments
Recommend psychotropic
drugs
SECTION 26  Psychiatric and drug-related disorders
6538
FURTHER READING
Aitken P, et  al. (2016). A history of liaison psychiatry in the UK.
BJPsych Bull, 40, 199–​203.
Fossey M, Tutty C (2012). Liaison psychiatry in the modern NHS
Michael Parsonage. Centre for Mental Health, London.
Naylor C, et al. (2016). Bringing together physical and mental health.
King’s Fund, London.
Sharpe M (2014). Psychological medicine and the future of psychiatry
(2014). Br J Psychiatry, 204, 91–​2.
SECTION 27
Forensic medicine
Section editor: John D. Firth
27.1	 Forensic and legal medicine  6541
Jason Payne-​James, Paul Marks, Ralph Bouhaidar,
and Steven B. Karch